F16P1_RABIT
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 03-AUG-2022, entry version 140.
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 allosteric inhibitor.
CC AMP binding affects the turnover of bound substrate and not the
CC affinity for substrate. Fructose 2,6-bisphosphate acts as competitive
CC inhibitor. Fructose 2,6-bisphosphate and AMP have synergistic effects
CC (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}.
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DR PIR; S70469; S70469.
DR PDB; 1BK4; X-ray; 2.30 A; A=2-338.
DR PDBsum; 1BK4; -.
DR AlphaFoldDB; P00637; -.
DR SMR; P00637; -.
DR STRING; 9986.ENSOCUP00000016277; -.
DR iPTMnet; P00637; -.
DR PRIDE; P00637; -.
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; ISS:UniProtKB.
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:0016311; P:dephosphorylation; ISS:UniProtKB.
DR GO; GO:0006002; P:fructose 6-phosphate metabolic process; IDA:UniProtKB.
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 CDD; cd00354; FBPase; 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 PANTHER; PTHR11556; PTHR11556; 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 PROSITE; PS00124; FBPASE; 1.
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 161..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 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 TURN 278..281
FT /evidence="ECO:0007829|PDB:1BK4"
FT HELIX 282..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 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
