ID F16P1_RABIT Reviewed; 338 AA. AC P00637; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 24-NOV-2009, sequence version 4. DT 10-JUN-2026, entry version 148. DE RecName: Full=Fructose-1,6-bisphosphatase 1; DE Short=FBPase 1; DE EC=3.1.3.11 {ECO:0000269|PubMed:202200}; DE AltName: Full=D-fructose-1,6-bisphosphate 1-phosphohydrolase 1; DE AltName: Full=Liver FBPase; GN Name=FBP1; Synonyms=FBP; OS Oryctolagus cuniculus (Rabbit). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus. OX NCBI_TaxID=9986; RN [1] RP PROTEIN SEQUENCE OF 2-338. RC TISSUE=Liver; RX PubMed=8766709; DOI=10.1016/0014-5793(96)00594-7; RA Kaiser R., Olsson H., Erman M., Weeks C.M., Hjelmqvist L., Ghosh D., RA Joernvall H.; RT "Fructose-1,6-bisphosphatase. Primary structure of the rabbit liver enzyme. RT 'Intermediate' variability of an oligomeric protein."; RL FEBS Lett. 389:249-252(1996). RN [2] RP PROTEIN SEQUENCE OF 2-19, AND ACETYLATION AT ALA-2. RC STRAIN=New Zealand white; TISSUE=Liver; RX PubMed=189691; DOI=10.1016/0003-9861(77)90185-0; RA El-Dorry H.A., Chu D.K., Dzugaj A., Tsolas O., Pontremoli S., RA Horecker B.L.; RT "Rabbit liver fructose 1,6-bisphosphatase: the sequence of the amino- RT terminal region."; RL Arch. Biochem. Biophys. 178:200-207(1977). RN [3] RP PROTEIN SEQUENCE OF 17-61. RC STRAIN=New Zealand white; TISSUE=Liver; RX PubMed=197893; DOI=10.1016/0003-9861(77)90558-6; RA El-Dorry H.A., Chu D.K., Dzugaj A., Botelho L.H., Pontremoli S., RA Horecker B.L.; RT "Primary structure of the S-peptide formed by digestion of rabbit liver RT fructose 1,6-biphosphatase with subtilisin."; RL Arch. Biochem. Biophys. 182:763-773(1977). RN [4] RP PROTEIN SEQUENCE OF 20-78, SUBUNIT, AND CATALYTIC ACTIVITY. RC STRAIN=New Zealand white; TISSUE=Liver; RX PubMed=202200; DOI=10.1016/0003-9861(77)90463-5; RA Botelho L.H., El-Dorry H.A., Crivellaro O., Chu D.K., Pontremoli S., RA Horecker B.L.; RT "Digestion of rabbit liver fructose 1,6-bisphosphatase with subtilisin: RT sites of cleavage and activity of the modified enzyme."; RL Arch. Biochem. Biophys. 184:535-545(1977). RN [5] RP PRELIMINARY PROTEIN SEQUENCE OF 84-123 AND 136-155, AND ALLOSTERIC RP REGULATION. RC TISSUE=Liver; RX PubMed=6289748; DOI=10.1016/0003-9861(82)90473-8; RA Suda H., Xu G.-J., Kutny R.M., Natalini P., Pontremoli S., Horecker B.L.; RT "Location of lysyl residues at the allosteric site of fructose 1,6- RT bisphosphatase."; RL Arch. Biochem. Biophys. 217:10-14(1982). RN [6] RP PROTEIN SEQUENCE OF 249-289 AND 296-338. RC TISSUE=Liver; RX PubMed=6284034; DOI=10.1016/0003-9861(82)90075-3; RA Xu G.J., Natalini P., Suda H., Tsolas O., Dzugaj A., Sun S.C., RA Pontremoli S., Horecker B.L.; RT "Rabbit liver fructose-1,6-bisphosphatase: location of an active site lysyl RT residue in the COOH-terminal fragment generated by a lysosomal RT proteinase."; RL Arch. Biochem. Biophys. 214:688-694(1982). RN [7] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH MAGNESIUM IONS. RX PubMed=10089399; DOI=10.1107/s0907444998008750; RA Weeks C.M., Roszak A.W., Erman M., Kaiser R., Joernvall H., Ghosh D.; RT "Structure of rabbit liver fructose 1,6-bisphosphatase at 2.3 A RT resolution."; RL Acta Crystallogr. D 55:93-102(1999). 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:0000269|PubMed:202200}; 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:0000269|PubMed:202200}. 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; S70469; S70469. DR PDB; 1BK4; X-ray; 2.30 A; A=2-338. DR AlphaFoldDB; P00637; -. DR SMR; P00637; -. DR FunCoup; P00637; 579. DR STRING; 9986.ENSOCUP00000046019; -. DR iPTMnet; P00637; -. DR PaxDb; 9986-ENSOCUP00000046019; -. DR eggNOG; KOG1458; Eukaryota. DR InParanoid; P00637; -. DR SABIO-RK; P00637; -. DR UniPathway; UPA00138; -. DR EvolutionaryTrace; P00637; -. DR Proteomes; UP000001811; 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; IDA: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; IDA: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. DR PDBsum; 1BK4; -. PE 1: Evidence at protein level; KW 3D-structure; 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:189691, FT ECO:0000269|PubMed:8766709" FT CHAIN 2..338 FT /note="Fructose-1,6-bisphosphatase 1" FT /id="PRO_0000200501" 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:0000269|PubMed:10089399, FT ECO:0007744|PDB:1BK4" 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 BINDING 119 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:10089399, FT ECO:0007744|PDB:1BK4" 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:0000269|PubMed:10089399, FT ECO:0007744|PDB:1BK4" FT BINDING 141 FT /ligand="AMP" FT /ligand_id="ChEBI:CHEBI:456215" FT /evidence="ECO:0000250|UniProtKB:P00636" 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:0000269|PubMed:10089399, FT ECO:0007744|PDB:1BK4" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000269|PubMed:189691" FT MOD_RES 151 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q9QXD6" 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" FT CONFLICT 84 FT /note="N -> D (in Ref. 5; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 89 FT /note="S -> A (in Ref. 5; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 93 FT /note="C -> S (in Ref. 5; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 116..117 FT /note="VC -> SN (in Ref. 5; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 122..123 FT /note="DG -> VP (in Ref. 5; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 268 FT /note="N -> D (in Ref. 6; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 281 FT /note="E -> Q (in Ref. 6; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 284 FT /note="Missing (in Ref. 6; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 301 FT /note="E -> Q (in Ref. 6; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 308..313 FT /note="PTDIHQ -> QTPDH (in Ref. 6; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 327 FT /note="E -> Q (in Ref. 6; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 330..331 FT /note="Missing (in Ref. 6; AA sequence)" FT /evidence="ECO:0000305" FT HELIX 14..25 FT /evidence="ECO:0007829|PDB:1BK4" FT HELIX 30..49 FT /evidence="ECO:0007829|PDB:1BK4" FT TURN 50..53 FT /evidence="ECO:0007829|PDB:1BK4" FT HELIX 74..88 FT /evidence="ECO:0007829|PDB:1BK4" FT STRAND 92..97 FT /evidence="ECO:0007829|PDB:1BK4" FT HELIX 108..110 FT /evidence="ECO:0007829|PDB:1BK4" FT STRAND 111..122 FT /evidence="ECO:0007829|PDB:1BK4" FT HELIX 126..129 FT /evidence="ECO:0007829|PDB:1BK4" FT STRAND 133..141 FT /evidence="ECO:0007829|PDB:1BK4" FT HELIX 150..153 FT /evidence="ECO:0007829|PDB:1BK4" FT HELIX 157..159 FT /evidence="ECO:0007829|PDB:1BK4" FT STRAND 160..178 FT /evidence="ECO:0007829|PDB:1BK4" FT STRAND 181..188 FT /evidence="ECO:0007829|PDB:1BK4" FT TURN 189..192 FT /evidence="ECO:0007829|PDB:1BK4" FT STRAND 193..198 FT /evidence="ECO:0007829|PDB:1BK4" FT STRAND 208..211 FT /evidence="ECO:0007829|PDB:1BK4" FT HELIX 214..219 FT /evidence="ECO:0007829|PDB:1BK4" FT HELIX 222..232 FT /evidence="ECO:0007829|PDB:1BK4" FT HELIX 239..241 FT /evidence="ECO:0007829|PDB:1BK4" FT HELIX 249..259 FT /evidence="ECO:0007829|PDB:1BK4" FT STRAND 262..265 FT /evidence="ECO:0007829|PDB:1BK4" FT STRAND 275..277 FT /evidence="ECO:0007829|PDB:1BK4" FT HELIX 278..282 FT /evidence="ECO:0007829|PDB:1BK4" FT HELIX 283..292 FT /evidence="ECO:0007829|PDB:1BK4" FT STRAND 295..297 FT /evidence="ECO:0007829|PDB:1BK4" FT STRAND 299..302 FT /evidence="ECO:0007829|PDB:1BK4" FT HELIX 303..305 FT /evidence="ECO:0007829|PDB:1BK4" FT HELIX 306..308 FT /evidence="ECO:0007829|PDB:1BK4" FT STRAND 317..320 FT /evidence="ECO:0007829|PDB:1BK4" FT HELIX 322..333 FT /evidence="ECO:0007829|PDB:1BK4" FT TURN 334..336 FT /evidence="ECO:0007829|PDB:1BK4" SQ SEQUENCE 338 AA; 36578 MW; 2676BF5964461250 CRC64; MADKAPFDTD ISTMTRFVME EGRKAGGTGE MTQLLNSLCT AVKAISTAVR KAGIAHLYGI AGSTNVTGDQ VKKLDVLSND LVMNMLKSSF ATCVLVSEED KNAIIVEPEK RGKYVVCFDP LDGSSNIDCL VSIGTIFGIY RKKSTDEPST KDALQPGRNL VAAGYALYGS ATMLVLAGGS GVNSFMLDPA IGEFILVDKN VKIKKKGNIY SLNEGYAKDF DPAVTEYIQK KKFPPDNSSP YGARYVGSMV ADVHRTLVYG GIFLYPANKK SPDGKLRLLY ECNPMAFIME KAGGMATTGK EAILDIVPTD IHQRAPVILG SPDDVQEFLE IYKKHAVK //