F16P1_RAT
ID F16P1_RAT Reviewed; 363 AA.
AC P19112; Q64594;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Fructose-1,6-bisphosphatase 1;
DE Short=FBPase 1;
DE EC=3.1.3.11 {ECO:0000269|PubMed:1313010};
DE AltName: Full=D-fructose-1,6-bisphosphate 1-phosphohydrolase 1;
DE AltName: Full=Liver FBPase;
GN Name=Fbp1; Synonyms=Fbp;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Liver;
RX PubMed=2847161; DOI=10.1073/pnas.85.22.8430;
RA El-Maghrabi M.R., Pilkis J., Marker A.J., Colosia A.D., D'Angelo G.,
RA Fraser B.A., Pilkis S.J.;
RT "cDNA sequence of rat liver fructose-1,6-bisphosphatase and evidence for
RT down-regulation of its mRNA by insulin.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:8430-8434(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Sprague-Dawley;
RX PubMed=1846613; DOI=10.1016/s0021-9258(18)52217-1;
RA El-Maghrabi M.R., Lange A.J., Kummel L., Pilkis S.J.;
RT "The rat fructose-1,6-bisphosphatase gene. Structure and regulation of
RT expression.";
RL J. Biol. Chem. 266:2115-2120(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7589895; DOI=10.1046/j.1432-0436.1995.5910051.x;
RA Bertolotti R., Armbruster-Hilbert L., Okayama H.;
RT "Liver fructose-1,6-bisphosphatase cDNA: trans-complementation of fission
RT yeast and characterization of two human transcripts.";
RL Differentiation 59:51-60(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 320-362.
RC TISSUE=Liver;
RX PubMed=6305949; DOI=10.1016/s0021-9258(18)32228-2;
RA Rittenhouse J., Chatterjee T., Marcus F., Reardon I., Heinrikson R.L.;
RT "Amino acid sequence of the COOH-terminal region of fructose-1,6-
RT bisphosphatases in relation to cyclic AMP-dependent phosphorylation.";
RL J. Biol. Chem. 258:7648-7652(1983).
RN [6]
RP CATALYTIC ACTIVITY, MUTAGENESIS OF LYS-275, AND ACTIVITY REGULATION.
RX PubMed=1313010; DOI=10.1016/s0021-9258(19)50459-8;
RA el-Maghrabi M.R., Austin L.R., Correia J.J., Pilkis S.J.;
RT "Lysine 274 is essential for fructose 2,6-bisphosphate inhibition of
RT fructose-1,6-bisphosphatase.";
RL J. Biol. Chem. 267:6526-6530(1992).
RN [7]
RP ACETYLATION AT VAL-2.
RX PubMed=19651254; DOI=10.1016/j.jprot.2009.07.008;
RA Novak E.M., Lee E.K., Innis S.M., Keller B.O.;
RT "Identification of novel protein targets regulated by maternal dietary
RT fatty acid composition in neonatal rat liver.";
RL J. Proteomics 73:41-49(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-216; SER-339 AND SER-353, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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:1313010};
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 {ECO:0000269|PubMed:1313010}.
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 EMBL; J04112; AAA60739.1; -; mRNA.
DR EMBL; M57284; AAA41131.1; -; Genomic_DNA.
DR EMBL; M57274; AAA41131.1; JOINED; Genomic_DNA.
DR EMBL; M57279; AAA41131.1; JOINED; Genomic_DNA.
DR EMBL; M57278; AAA41131.1; JOINED; Genomic_DNA.
DR EMBL; M57282; AAA41131.1; JOINED; Genomic_DNA.
DR EMBL; M57281; AAA41131.1; JOINED; Genomic_DNA.
DR EMBL; M86240; AAA86425.1; -; mRNA.
DR EMBL; BC078894; AAH78894.1; -; mRNA.
DR EMBL; BC078895; AAH78895.1; -; mRNA.
DR PIR; A31342; A31342.
DR RefSeq; NP_036690.2; NM_012558.3.
DR AlphaFoldDB; P19112; -.
DR SMR; P19112; -.
DR STRING; 10116.ENSRNOP00000023685; -.
DR BindingDB; P19112; -.
DR ChEMBL; CHEMBL4391; -.
DR iPTMnet; P19112; -.
DR PhosphoSitePlus; P19112; -.
DR PRIDE; P19112; -.
DR Ensembl; ENSRNOT00000023685; ENSRNOP00000023685; ENSRNOG00000017597.
DR GeneID; 24362; -.
DR KEGG; rno:24362; -.
DR UCSC; RGD:2595; rat.
DR CTD; 2203; -.
DR RGD; 2595; Fbp1.
DR eggNOG; KOG1458; Eukaryota.
DR GeneTree; ENSGT00390000015513; -.
DR InParanoid; P19112; -.
DR OrthoDB; 1381522at2759; -.
DR PhylomeDB; P19112; -.
DR BRENDA; 3.1.3.11; 5301.
DR Reactome; R-RNO-70263; Gluconeogenesis.
DR SABIO-RK; P19112; -.
DR UniPathway; UPA00138; -.
DR PRO; PR:P19112; -.
DR Proteomes; UP000002494; Chromosome 17.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0016208; F:AMP binding; ISS:UniProtKB.
DR GO; GO:0042132; F:fructose 1,6-bisphosphate 1-phosphatase activity; IDA:RGD.
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; IDA:RGD.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0005975; P:carbohydrate metabolic process; IDA:RGD.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEP:RGD.
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:0030388; P:fructose 1,6-bisphosphate metabolic process; IBA:GO_Central.
DR GO; GO:0006002; P:fructose 6-phosphate metabolic process; IDA:RGD.
DR GO; GO:0006000; P:fructose metabolic process; IBA:GO_Central.
DR GO; GO:0006094; P:gluconeogenesis; IDA:RGD.
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:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0006111; P:regulation of gluconeogenesis; ISS:UniProtKB.
DR GO; GO:0005986; P:sucrose biosynthetic process; IBA:GO_Central.
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 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:19651254,
FT ECO:0000269|PubMed:2847161"
FT CHAIN 2..363
FT /note="Fructose-1,6-bisphosphatase 1"
FT /id="PRO_0000200502"
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|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:0000250|UniProtKB:P00636"
FT MOD_RES 2
FT /note="N-acetylvaline"
FT /evidence="ECO:0000269|PubMed:19651254"
FT MOD_RES 151
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9QXD6"
FT MOD_RES 216
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:22673903"
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 MOD_RES 339
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 353
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MUTAGEN 275
FT /note="K->A: Reduces affinity for substrate 20-fold, and
FT decreases affinity for the competitive inhibitor fructose
FT 2,6-bisphosphate 500-fold."
FT /evidence="ECO:0000269|PubMed:1313010"
FT CONFLICT 148
FT /note="P -> A (in Ref. 2; AAA41131)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 363 AA; 39609 MW; 0470F1A2EA917D6F CRC64;
MVDHAPFETD ISTLTRFVLE EGRKAGGTGE MTQLLNSLCT AIKAISSAVR QAGIAQLYGI
AGSTNVTGDQ VKKLDILSND LVINMLKSSY ATCVLVSEED THAIIIEPEK RGKYVVCFDP
LDGSSNIDCL ASIGTIFGIY RKTSANEPSE KDALQPGRNL VAAGYALYGS ATMLVLAMNC
GVNCFMLDPS IGEFILVDRD VKIKKKGNIY SINEGYAKDF DPAINEYIQR KKFPPDNSAP
YGARYVGSMV ADVHRTLVYG GIFLYPANKK NPSGKLRLLY ECNPIAYVME KAGGLATTGN
EDILDIVPTE IHQKAPVIMG STEDVQEFLE IYNKDKAKSR PSLPLPQSRA RESPVHSICD
ELF
