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Protein

Fructose-1,6-bisphosphatase 1

Gene

FBP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.3 Publications

Catalytic activityi

D-fructose 1,6-bisphosphate + H2O = D-fructose 6-phosphate + phosphate.2 Publications

Cofactori

Mg2+1 PublicationNote: Binds 3 Mg2+ ions per subunit.By similarity

Activity regulationi

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.5 Publications

Kineticsi

The kinetic constants are determined for the recombinant enzyme expressed in E.coli.
  1. KM=2.7 µM for fructose 1,6-biphosphate1 Publication

    Pathwayi: gluconeogenesis

    This protein is involved in the pathway gluconeogenesis, which is part of Carbohydrate biosynthesis.
    View all proteins of this organism that are known to be involved in the pathway gluconeogenesis and in Carbohydrate biosynthesis.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Metal bindingi69Magnesium 1By similarity1
    Metal bindingi98Magnesium 1By similarity1
    Metal bindingi98Magnesium 2By similarity1
    Metal bindingi119Magnesium 2By similarity1
    Metal bindingi119Magnesium 3Combined sources1
    Metal bindingi121Magnesium 2; via carbonyl oxygenBy similarity1
    Metal bindingi122Magnesium 3Combined sources1
    Binding sitei141AMPCombined sources1 Publication1
    Binding sitei265SubstrateBy similarity1
    Metal bindingi281Magnesium 3Combined sources1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi18 – 22AMPCombined sources1 Publication5
    Nucleotide bindingi28 – 32AMPCombined sources1 Publication5
    Nucleotide bindingi113 – 114AMPCombined sources1 Publication2

    GO - Molecular functioni

    • AMP binding Source: UniProtKB
    • fructose 1,6-bisphosphate 1-phosphatase activity Source: UniProtKB
    • identical protein binding Source: IntAct
    • metal ion binding Source: UniProtKB
    • monosaccharide binding Source: UniProtKB

    GO - Biological processi

    Keywordsi

    Molecular functionAllosteric enzyme, Hydrolase
    Biological processCarbohydrate metabolism, Gluconeogenesis
    LigandMagnesium, Metal-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS09189-MONOMER
    BRENDAi3.1.3.11 2681
    ReactomeiR-HSA-70263 Gluconeogenesis
    SABIO-RKiP09467
    UniPathwayi
    UPA00138

    Protein family/group databases

    MoonProtiP09467

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Fructose-1,6-bisphosphatase 1 (EC:3.1.3.112 Publications)
    Short name:
    FBPase 1
    Alternative name(s):
    D-fructose-1,6-bisphosphate 1-phosphohydrolase 1
    Liver FBPase
    Gene namesi
    Name:FBP1
    Synonyms:FBP
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 9

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000165140.9
    HGNCiHGNC:3606 FBP1
    MIMi611570 gene
    neXtProtiNX_P09467

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Pathology & Biotechi

    Involvement in diseasei

    Fructose-1,6-bisphosphatase deficiency (FBP1D)3 Publications
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionAn autosomal recessive metabolic disorder characterized by impaired gluconeogenesis, and episodes of hypoglycemia and metabolic acidosis that can be lethal in newborn infants or young children.
    See also OMIM:229700
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_075492158R → W in FBP1D; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs766005419EnsemblClinVar.1
    Natural variantiVAR_002380164G → S in FBP1D. 1 PublicationCorresponds to variant dbSNP:rs121918188EnsemblClinVar.1
    Natural variantiVAR_002381177A → D in FBP1D. 1 PublicationCorresponds to variant dbSNP:rs121918189EnsemblClinVar.1
    Natural variantiVAR_038812194F → S in FBP1D. 1 PublicationCorresponds to variant dbSNP:rs121918191EnsemblClinVar.1
    Natural variantiVAR_038813284P → R in FBP1D. 1 PublicationCorresponds to variant dbSNP:rs121918192EnsemblClinVar.1

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi70Q → E: Increased affinity towards Ca(2+) and Mg(2+). 1 Publication1
    Mutagenesisi119D → A: Reduced activity. 1 Publication1
    Mutagenesisi122D → A: Reduced activity. 1 Publication1

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    DisGeNETi2203
    MalaCardsiFBP1
    MIMi229700 phenotype
    OpenTargetsiENSG00000165140
    Orphaneti348 Fructose-1,6-bisphosphatase deficiency
    PharmGKBiPA28018

    Chemistry databases

    ChEMBLiCHEMBL3975
    DrugBankiDB08484 4-AMINO-N-[(2-SULFANYLETHYL)CARBAMOYL]BENZENESULFONAMIDE
    DB00131 Adenosine monophosphate
    DB04493 Fructose-6-Phosphate
    DB05053 MB07803
    DB04175 Mdl-29951

    Polymorphism and mutation databases

    BioMutaiFBP1
    DMDMi311033495

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemovedBy similarity1 Publication
    ChainiPRO_00002004982 – 338Fructose-1,6-bisphosphatase 1Add BLAST337

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei2N-acetylalanineBy similarity1
    Modified residuei151N6-succinyllysineBy similarity1
    Modified residuei216PhosphotyrosineBy similarity1
    Modified residuei245PhosphotyrosineBy similarity1
    Modified residuei265PhosphotyrosineCombined sources1

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    EPDiP09467
    MaxQBiP09467
    PaxDbiP09467
    PeptideAtlasiP09467
    PRIDEiP09467
    ProteomicsDBi52223

    PTM databases

    DEPODiP09467
    iPTMnetiP09467
    PhosphoSitePlusiP09467

    Expressioni

    Tissue specificityi

    Expressed in pancreatic islets.1 Publication

    Inductioni

    Up-regulated in pancreatic islets of individuals with type 2 diabetes.1 Publication

    Gene expression databases

    BgeeiENSG00000165140 Expressed in 153 organ(s), highest expression level in right lobe of liver
    CleanExiHS_FBP1
    ExpressionAtlasiP09467 baseline and differential
    GenevisibleiP09467 HS

    Organism-specific databases

    HPAiCAB033869
    HPA005857
    HPA012513

    Interactioni

    Subunit structurei

    Homotetramer.4 Publications

    Binary interactionsi

    GO - Molecular functioni

    Protein-protein interaction databases

    BioGridi108497, 31 interactors
    DIPiDIP-46677N
    IntActiP09467, 39 interactors
    MINTiP09467
    STRINGi9606.ENSP00000364475

    Chemistry databases

    BindingDBiP09467

    Structurei

    Secondary structure

    1338
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    ProteinModelPortaliP09467
    SMRiP09467
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP09467

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni122 – 125Substrate bindingBy similarity4
    Regioni213 – 216Substrate bindingBy similarity4
    Regioni244 – 249Substrate bindingBy similarity6
    Regioni275 – 277Substrate bindingBy similarity3

    Sequence similaritiesi

    Belongs to the FBPase class 1 family.Curated

    Phylogenomic databases

    eggNOGiKOG1458 Eukaryota
    COG0158 LUCA
    GeneTreeiENSGT00390000015513
    HOGENOMiHOG000191265
    HOVERGENiHBG005627
    InParanoidiP09467
    KOiK03841
    OMAiQSGLVCR
    OrthoDBiEOG091G0AZP
    PhylomeDBiP09467
    TreeFamiTF314824

    Family and domain databases

    CDDicd00354 FBPase, 1 hit
    HAMAPiMF_01855 FBPase_class1, 1 hit
    InterProiView protein in InterPro
    IPR000146 FBPase_class-1
    IPR033391 FBPase_N
    IPR028343 FBPtase
    IPR020548 Fructose_bisphosphatase_AS
    PANTHERiPTHR11556 PTHR11556, 1 hit
    PfamiView protein in Pfam
    PF00316 FBPase, 1 hit
    PIRSFiPIRSF500210 FBPtase, 1 hit
    PIRSF000904 FBPtase_SBPase, 1 hit
    PRINTSiPR00115 F16BPHPHTASE
    PROSITEiView protein in PROSITE
    PS00124 FBPASE, 1 hit

    Sequence (1+)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

    P09467-1 [UniParc]FASTAAdd to basket
    « Hide
            10         20         30         40         50
    MADQAPFDTD VNTLTRFVME EGRKARGTGE LTQLLNSLCT AVKAISSAVR
    60 70 80 90 100
    KAGIAHLYGI AGSTNVTGDQ VKKLDVLSND LVMNMLKSSF ATCVLVSEED
    110 120 130 140 150
    KHAIIVEPEK RGKYVVCFDP LDGSSNIDCL VSVGTIFGIY RKKSTDEPSE
    160 170 180 190 200
    KDALQPGRNL VAAGYALYGS ATMLVLAMDC GVNCFMLDPA IGEFILVDKD
    210 220 230 240 250
    VKIKKKGKIY SLNEGYARDF DPAVTEYIQR KKFPPDNSAP YGARYVGSMV
    260 270 280 290 300
    ADVHRTLVYG GIFLYPANKK SPNGKLRLLY ECNPMAYVME KAGGMATTGK
    310 320 330
    EAVLDVIPTD IHQRAPVILG SPDDVLEFLK VYEKHSAQ
    Length:338
    Mass (Da):36,842
    Last modified:November 2, 2010 - v5
    Checksum:iB3D270BCBB358B71
    GO

    Computationally mapped potential isoform sequencesi

    There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    Q5VZC3Q5VZC3_HUMAN
    Fructose-1,6-bisphosphatase 1
    FBP1
    151Annotation score:

    Sequence cautioni

    The sequence AAC50207 differs from that shown. Reason: Erroneous gene model prediction.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti215G → A in AAA35817 (PubMed:8387495).Curated1
    Sequence conflicti215G → A in AAC25774 (PubMed:10222032).Curated1
    Sequence conflicti337A → G in AAC25774 (PubMed:10222032).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_075492158R → W in FBP1D; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs766005419EnsemblClinVar.1
    Natural variantiVAR_002380164G → S in FBP1D. 1 PublicationCorresponds to variant dbSNP:rs121918188EnsemblClinVar.1
    Natural variantiVAR_002381177A → D in FBP1D. 1 PublicationCorresponds to variant dbSNP:rs121918189EnsemblClinVar.1
    Natural variantiVAR_038812194F → S in FBP1D. 1 PublicationCorresponds to variant dbSNP:rs121918191EnsemblClinVar.1
    Natural variantiVAR_022212218R → K7 PublicationsCorresponds to variant dbSNP:rs1769259EnsemblClinVar.1
    Natural variantiVAR_022213233F → I1 PublicationCorresponds to variant dbSNP:rs2297085EnsemblClinVar.1
    Natural variantiVAR_022214255R → L1 PublicationCorresponds to variant dbSNP:rs28369761Ensembl.1
    Natural variantiVAR_038813284P → R in FBP1D. 1 PublicationCorresponds to variant dbSNP:rs121918192EnsemblClinVar.1
    Natural variantiVAR_002382325V → A1 Publication1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M19922 mRNA Translation: AAA35517.1
    L10320 mRNA Translation: AAA35817.1
    D26054 mRNA Translation: BAA05051.1
    D26055 mRNA Translation: BAA05052.1
    D26056 mRNA Translation: BAA05053.1
    U21931
    , U21925, U21926, U21927, U21929, U21930 Genomic DNA Translation: AAC50207.1 Sequence problems.
    AF073475 mRNA Translation: AAC25774.1
    AK223395 mRNA Translation: BAD97115.1
    AY866483 Genomic DNA Translation: AAW34363.1
    AL161728 Genomic DNA No translation available.
    BC012927 mRNA Translation: AAH12927.1
    U47919 mRNA Translation: AAA89098.1
    U47918 mRNA Translation: AAA89097.1
    CCDSiCCDS6712.1
    PIRiA46666
    RefSeqiNP_000498.2, NM_000507.3
    NP_001121100.1, NM_001127628.1
    UniGeneiHs.494496

    Genome annotation databases

    EnsembliENST00000375326; ENSP00000364475; ENSG00000165140
    ENST00000415431; ENSP00000408025; ENSG00000165140
    GeneIDi2203
    KEGGihsa:2203
    UCSCiuc004auw.5 human

    Keywords - Coding sequence diversityi

    Polymorphism

    Similar proteinsi

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs
    Wikipedia

    Fructose bisphosphatase entry

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M19922 mRNA Translation: AAA35517.1
    L10320 mRNA Translation: AAA35817.1
    D26054 mRNA Translation: BAA05051.1
    D26055 mRNA Translation: BAA05052.1
    D26056 mRNA Translation: BAA05053.1
    U21931
    , U21925, U21926, U21927, U21929, U21930 Genomic DNA Translation: AAC50207.1 Sequence problems.
    AF073475 mRNA Translation: AAC25774.1
    AK223395 mRNA Translation: BAD97115.1
    AY866483 Genomic DNA Translation: AAW34363.1
    AL161728 Genomic DNA No translation available.
    BC012927 mRNA Translation: AAH12927.1
    U47919 mRNA Translation: AAA89098.1
    U47918 mRNA Translation: AAA89097.1
    CCDSiCCDS6712.1
    PIRiA46666
    RefSeqiNP_000498.2, NM_000507.3
    NP_001121100.1, NM_001127628.1
    UniGeneiHs.494496

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1FTAX-ray2.30A/B/C/D2-338[»]
    2FHYX-ray2.95A/D/H/L1-338[»]
    2FIEX-ray2.81A/D/H/L1-338[»]
    2FIXX-ray3.50A/D/H/L1-338[»]
    2JJKX-ray2.00A/B/C/D1-338[»]
    2VT5X-ray2.20A/B/C/D/E/F/G/H1-338[»]
    2WBBX-ray2.22A/B/C/D/E/F/G/H1-338[»]
    2WBDX-ray2.40A/B/C/D/E/F/G/H1-338[»]
    2Y5KX-ray2.10A/B/C/D1-338[»]
    2Y5LX-ray2.20A/B/C/D/E/F/G/H1-338[»]
    3A29X-ray2.60A/B/C/D2-338[»]
    3KBZX-ray2.45A/B/C/D2-338[»]
    3KC0X-ray2.80A/B/C/D2-338[»]
    3KC1X-ray2.25A/B/C/D2-338[»]
    4MJOX-ray2.40A/B/C/D/E/F/G/H1-338[»]
    5LDZX-ray2.20A/B/C/D/E/F1-338[»]
    ProteinModelPortaliP09467
    SMRiP09467
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi108497, 31 interactors
    DIPiDIP-46677N
    IntActiP09467, 39 interactors
    MINTiP09467
    STRINGi9606.ENSP00000364475

    Chemistry databases

    BindingDBiP09467
    ChEMBLiCHEMBL3975
    DrugBankiDB08484 4-AMINO-N-[(2-SULFANYLETHYL)CARBAMOYL]BENZENESULFONAMIDE
    DB00131 Adenosine monophosphate
    DB04493 Fructose-6-Phosphate
    DB05053 MB07803
    DB04175 Mdl-29951

    Protein family/group databases

    MoonProtiP09467

    PTM databases

    DEPODiP09467
    iPTMnetiP09467
    PhosphoSitePlusiP09467

    Polymorphism and mutation databases

    BioMutaiFBP1
    DMDMi311033495

    Proteomic databases

    EPDiP09467
    MaxQBiP09467
    PaxDbiP09467
    PeptideAtlasiP09467
    PRIDEiP09467
    ProteomicsDBi52223

    Protocols and materials databases

    DNASUi2203
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000375326; ENSP00000364475; ENSG00000165140
    ENST00000415431; ENSP00000408025; ENSG00000165140
    GeneIDi2203
    KEGGihsa:2203
    UCSCiuc004auw.5 human

    Organism-specific databases

    CTDi2203
    DisGeNETi2203
    EuPathDBiHostDB:ENSG00000165140.9
    GeneCardsiFBP1
    H-InvDBiHIX0008191
    HGNCiHGNC:3606 FBP1
    HPAiCAB033869
    HPA005857
    HPA012513
    MalaCardsiFBP1
    MIMi229700 phenotype
    611570 gene
    neXtProtiNX_P09467
    OpenTargetsiENSG00000165140
    Orphaneti348 Fructose-1,6-bisphosphatase deficiency
    PharmGKBiPA28018
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1458 Eukaryota
    COG0158 LUCA
    GeneTreeiENSGT00390000015513
    HOGENOMiHOG000191265
    HOVERGENiHBG005627
    InParanoidiP09467
    KOiK03841
    OMAiQSGLVCR
    OrthoDBiEOG091G0AZP
    PhylomeDBiP09467
    TreeFamiTF314824

    Enzyme and pathway databases

    UniPathwayi
    UPA00138

    BioCyciMetaCyc:HS09189-MONOMER
    BRENDAi3.1.3.11 2681
    ReactomeiR-HSA-70263 Gluconeogenesis
    SABIO-RKiP09467

    Miscellaneous databases

    ChiTaRSiFBP1 human
    EvolutionaryTraceiP09467
    GenomeRNAii2203
    PROiPR:P09467
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000165140 Expressed in 153 organ(s), highest expression level in right lobe of liver
    CleanExiHS_FBP1
    ExpressionAtlasiP09467 baseline and differential
    GenevisibleiP09467 HS

    Family and domain databases

    CDDicd00354 FBPase, 1 hit
    HAMAPiMF_01855 FBPase_class1, 1 hit
    InterProiView protein in InterPro
    IPR000146 FBPase_class-1
    IPR033391 FBPase_N
    IPR028343 FBPtase
    IPR020548 Fructose_bisphosphatase_AS
    PANTHERiPTHR11556 PTHR11556, 1 hit
    PfamiView protein in Pfam
    PF00316 FBPase, 1 hit
    PIRSFiPIRSF500210 FBPtase, 1 hit
    PIRSF000904 FBPtase_SBPase, 1 hit
    PRINTSiPR00115 F16BPHPHTASE
    PROSITEiView protein in PROSITE
    PS00124 FBPASE, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiF16P1_HUMAN
    AccessioniPrimary (citable) accession number: P09467
    Secondary accession number(s): O75571, Q53F94, Q96E46
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
    Last sequence update: November 2, 2010
    Last modified: November 7, 2018
    This is version 203 of the entry and version 5 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. Human chromosome 9
      Human chromosome 9: entries, gene names and cross-references to MIM
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