ID F16P1_SHEEP Reviewed; 337 AA. AC P09199; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 28-JAN-2026, entry version 130. DE RecName: Full=Fructose-1,6-bisphosphatase 1; DE Short=FBPase 1; DE EC=3.1.3.11 {ECO:0000250|UniProtKB:P19112}; DE AltName: Full=D-fructose-1,6-bisphosphate 1-phosphohydrolase 1; DE AltName: Full=Liver FBPase; GN Name=FBP1; Synonyms=FBP; OS Ovis aries (Sheep). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Caprinae; Ovis. OX NCBI_TaxID=9940; RN [1] RP PROTEIN SEQUENCE OF 2-337, ACETYLATION AT THR-2, AND PHOSPHORYLATION AT RP SER-208. RX PubMed=6316885; DOI=10.1071/bi9830235; RA Fisher W.K., Thompson E.O.P.; RT "Amino acid sequence studies on sheep liver fructose-bisphosphatase. II. RT The complete sequence."; RL Aust. J. Biol. Sci. 36:235-250(1983). RN [2] RP PROTEIN SEQUENCE OF 2-61, AND ACETYLATION AT THR-2. RX PubMed=6264908; DOI=10.1071/bi9800665; RA Fisher W.K., Thompson E.O.P.; RT "Amino acid sequence studies on sheep liver fructose-bisphosphatase. I. The RT S-peptide."; RL Aust. J. Biol. Sci. 33:665-674(1980). CC -!- FUNCTION: Catalyzes the hydrolysis of fructose 1,6-bisphosphate to CC fructose 6-phosphate in the presence of divalent cations, acting as a CC rate-limiting enzyme in gluconeogenesis. Plays a role in regulating CC glucose sensing and insulin secretion of pancreatic beta-cells. Appears CC to modulate glycerol gluconeogenesis in liver. Important regulator of CC appetite and adiposity; increased expression of the protein in liver CC after nutrient excess increases circulating satiety hormones and CC reduces appetite-stimulating neuropeptides and thus seems to provide a CC feedback mechanism to limit weight gain. CC {ECO:0000250|UniProtKB:P09467}. CC -!- CATALYTIC ACTIVITY: CC Reaction=beta-D-fructose 1,6-bisphosphate + H2O = beta-D-fructose 6- CC phosphate + phosphate; Xref=Rhea:RHEA:11064, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:32966, ChEBI:CHEBI:43474, ChEBI:CHEBI:57634; EC=3.1.3.11; CC Evidence={ECO:0000250|UniProtKB:P19112}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:P00636}; CC Note=Binds 3 Mg(2+) ions per subunit. {ECO:0000250|UniProtKB:P00636}; CC -!- ACTIVITY REGULATION: Subject to complex allosteric regulation. The CC enzyme can assume an active R-state, or an inactive T-state. CC Intermediate conformations may exist. AMP acts as an allosteric CC inhibitor. AMP binding affects the turnover of bound substrate and not CC the affinity for substrate. Fructose 2,6-bisphosphate acts as a CC competitive inhibitor. Fructose 2,6-bisphosphate and AMP have CC synergistic effects (By similarity). {ECO:0000250}. CC -!- PATHWAY: Carbohydrate biosynthesis; gluconeogenesis. CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P00636}. CC -!- SIMILARITY: Belongs to the FBPase class 1 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR PIR; A05318; A05318. DR AlphaFoldDB; P09199; -. DR SMR; P09199; -. DR STRING; 9940.ENSOARP00000009283; -. DR iPTMnet; P09199; -. DR PaxDb; 9940-ENSOARP00000009283; -. DR eggNOG; KOG1458; Eukaryota. DR UniPathway; UPA00138; -. DR Proteomes; UP000809102; Unplaced. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; IEA:TreeGrafter. DR GO; GO:0016208; F:AMP binding; ISS:UniProtKB. DR GO; GO:0042132; F:fructose 1,6-bisphosphate 1-phosphatase activity; ISS:UniProtKB. DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB. DR GO; GO:0046872; F:metal ion binding; ISS:UniProtKB. DR GO; GO:0048029; F:monosaccharide binding; ISS:UniProtKB. DR GO; GO:0071286; P:cellular response to magnesium ion; ISS:UniProtKB. DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; ISS:UniProtKB. DR GO; GO:0030388; P:fructose 1,6-bisphosphate metabolic process; IEA:TreeGrafter. DR GO; GO:0006002; P:fructose 6-phosphate metabolic process; ISS:UniProtKB. DR GO; GO:0006000; P:fructose metabolic process; IEA:TreeGrafter. DR GO; GO:0006094; P:gluconeogenesis; ISS:UniProtKB. DR GO; GO:0030308; P:negative regulation of cell growth; ISS:UniProtKB. DR GO; GO:0045820; P:negative regulation of glycolytic process; ISS:UniProtKB. DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; ISS:UniProtKB. DR GO; GO:0006111; P:regulation of gluconeogenesis; ISS:UniProtKB. DR GO; GO:0005986; P:sucrose biosynthetic process; IEA:TreeGrafter. DR CDD; cd00354; FBPase; 1. DR FunFam; 3.30.540.10:FF:000037; Fructose-1,6-bisphosphatase 1; 1. DR FunFam; 3.40.190.80:FF:000001; Fructose-1,6-bisphosphatase class 1; 1. DR Gene3D; 3.40.190.80; -; 1. DR Gene3D; 3.30.540.10; Fructose-1,6-Bisphosphatase, subunit A, domain 1; 1. DR HAMAP; MF_01855; FBPase_class1; 1. DR InterPro; IPR044015; FBPase_C_dom. DR InterPro; IPR000146; FBPase_class-1. DR InterPro; IPR033391; FBPase_N. DR InterPro; IPR028343; FBPtase. DR InterPro; IPR020548; Fructose_bisphosphatase_AS. DR NCBIfam; NF006778; PRK09293.1-1; 1. DR PANTHER; PTHR11556:SF11; FRUCTOSE-1,6-BISPHOSPHATASE 1; 1. DR PANTHER; PTHR11556; FRUCTOSE-1,6-BISPHOSPHATASE-RELATED; 1. DR Pfam; PF00316; FBPase; 1. DR Pfam; PF18913; FBPase_C; 1. DR PIRSF; PIRSF500210; FBPtase; 1. DR PIRSF; PIRSF000904; FBPtase_SBPase; 1. DR PRINTS; PR00115; F16BPHPHTASE. DR SUPFAM; SSF56655; Carbohydrate phosphatase; 1. DR PROSITE; PS00124; FBPASE; 1. PE 1: Evidence at protein level; KW Acetylation; Allosteric enzyme; Carbohydrate metabolism; KW Direct protein sequencing; Gluconeogenesis; Hydrolase; Magnesium; KW Metal-binding; Phosphoprotein; Reference proteome. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:6264908, FT ECO:0000269|PubMed:6316885" FT CHAIN 2..337 FT /note="Fructose-1,6-bisphosphatase 1" FT /id="PRO_0000200503" FT BINDING 18..22 FT /ligand="AMP" FT /ligand_id="ChEBI:CHEBI:456215" FT /evidence="ECO:0000250|UniProtKB:P00636" FT BINDING 28..32 FT /ligand="AMP" FT /ligand_id="ChEBI:CHEBI:456215" FT /evidence="ECO:0000250|UniProtKB:P00636" FT BINDING 69 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P00636" FT BINDING 98 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P00636" FT BINDING 98 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P00636" FT BINDING 113..114 FT /ligand="AMP" FT /ligand_id="ChEBI:CHEBI:456215" FT /evidence="ECO:0000250|UniProtKB:P00636" FT BINDING 119 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P00636" FT BINDING 119 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:P00636" FT BINDING 121 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P00636" FT BINDING 122..125 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P00636" FT BINDING 122 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:P00636" FT BINDING 141 FT /ligand="AMP" FT /ligand_id="ChEBI:CHEBI:456215" FT /evidence="ECO:0000250" FT BINDING 213..216 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P00636" FT BINDING 244..249 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P00636" FT BINDING 265 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P00636" FT BINDING 275..277 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P00636" FT BINDING 281 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:P00636" FT MOD_RES 2 FT /note="N-acetylthreonine" FT /evidence="ECO:0000269|PubMed:6264908, FT ECO:0000269|PubMed:6316885" FT MOD_RES 151 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q9QXD6" FT MOD_RES 208 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000269|PubMed:6316885" FT MOD_RES 216 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q9QXD6" FT MOD_RES 245 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q9QXD6" FT MOD_RES 265 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P09467" SQ SEQUENCE 337 AA; 36675 MW; 4477539DA1AF9334 CRC64; MTDEAPFDTN IVTVTRFVME EGRKARGTGE MTQLLNSLCT AVKAISTAVR KAGIAHLYGI AGTTNVTGDQ VKKLDVLSND LVVNVLKSSF ATCVLVSEED KHAIIVEPEK RGKYVVCFDP LDGSSNIDCL VSIGTIFGIY KKISKDDPSE KDALQPGRNL VAAGYALYGS ATMLVLAMVN GVNCFMLDPA IGEFILVDRD VKIKKKGSIY SLNEGYAKDF DPALTEYVQR KKFPPDNSAP YGSRYVGSMV ADVHRTLVYG GIFMYPADKK SPSGKLRLLY ECDPMAYVIE KAGGMATTGK EAVLDIVPTD IHQKVPIILG SPEDVTEFLE IKKYTAK //