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Protein

Fructose-1,6-bisphosphatase isozyme 2

Gene

FBP2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations and probably participates in glycogen synthesis from carbohydrate precursors, such as lactate.2 Publications

Catalytic activityi

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

Cofactori

Mg2+2 PublicationsNote: Binds 3 Mg2+ ions per subunit.2 Publications

Enzyme 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. Fructose 2,6-bisphosphate acts as competitive inhibitor. Strongly inhibited by Ca2+.3 Publications

Kineticsi

The kinetic constants are determined for the recombinant enzyme expressed in E.coli.

  1. KM=1.3 µM for fructose 1,6-bisphosphate2 Publications
  2. KM=2.6 µM for fructose 1,6-bisphosphate2 Publications

    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)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei18 – 181AMP; via carbonyl oxygen1 Publication
    Sitei33 – 331Important for the conversion from active R-state to inactive T-state in the presence of AMP
    Metal bindingi69 – 691Magnesium 1
    Metal bindingi98 – 981Magnesium 1
    Metal bindingi98 – 981Magnesium 2
    Metal bindingi119 – 1191Magnesium 2
    Metal bindingi119 – 1191Magnesium 3
    Metal bindingi121 – 1211Magnesium 2; via carbonyl oxygen
    Metal bindingi122 – 1221Magnesium 3
    Binding sitei122 – 1221Substrate
    Binding sitei141 – 1411AMP1 Publication
    Binding sitei265 – 2651Substrate
    Binding sitei275 – 2751Substrate
    Metal bindingi281 – 2811Magnesium 3

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi28 – 325AMP1 Publication
    Nucleotide bindingi113 – 1142AMP1 Publication

    GO - Molecular functioni

    GO - Biological processi

    • fructose metabolic process Source: ProtInc
    • gluconeogenesis Source: Reactome
    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Biological processi

    Carbohydrate metabolism, Gluconeogenesis

    Keywords - Ligandi

    Calcium, Magnesium, Metal-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS05462-MONOMER.
    ReactomeiR-HSA-70263. Gluconeogenesis.
    SABIO-RKO00757.
    UniPathwayiUPA00138.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Fructose-1,6-bisphosphatase isozyme 2 (EC:3.1.3.11)
    Short name:
    FBPase 2
    Alternative name(s):
    D-fructose-1,6-bisphosphate 1-phosphohydrolase 2
    Muscle FBPase
    Gene namesi
    Name:FBP2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 9

    Organism-specific databases

    HGNCiHGNC:3607. FBP2.

    Subcellular locationi

    • Cell junction By similarity
    • Cytoplasm
    • Nucleus
    • CytoplasmmyofibrilsarcomereZ line

    • Note: In neonatal cardiomyocytes, distributed throughout the cytosol, accumulating in the intercalated disks which occur at the Z line of cardiomyocytes and connect adjacent cells, and also located in the nucleus; dissociates from the Z line following an increase in cytosolic Ca2+ concentration (By similarity). In muscle precursor cells, localizes predominantly to the nucleus and to a lesser extent to the cytoplasm at the proliferative phase, while mainly localizing to the cytoplasm at the differentiation phase (By similarity). Colocalizes with ALDOA and alpha-actinin on both sides of the Z line of skeletal muscle; dissociates rapidly from the Z line following an increase in cytosolic Ca2+ concentration.By similarity

    GO - Cellular componenti

    • cell junction Source: UniProtKB-SubCell
    • cytosol Source: Reactome
    • extracellular exosome Source: UniProtKB
    • nucleus Source: UniProtKB-SubCell
    • Z disc Source: UniProtKB-SubCell
    Complete GO annotation...

    Keywords - Cellular componenti

    Cell junction, Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi1 – 1010Missing : Greatly reduces sensitivity to inhibition by AMP and Ca(2+) and activation by Mg(2+). Decreases binding to ALDOA. 1 Publication
    Mutagenesisi1 – 77Missing : Greatly reduces sensitivity to inhibition by AMP and Ca(2+) and activation by Mg(2+). Decreases binding to ALDOA.
    Mutagenesisi1 – 66Missing : Reduces sensitivity to inhibition by AMP and Ca(2+) and activation by Mg(2+). Decreases binding to ALDOA.
    Mutagenesisi1 – 55Missing : Reduces sensitivity to inhibition by AMP and Ca(2+) and activation by Mg(2+). Decreases binding to ALDOA.
    Mutagenesisi1 – 44Missing : Slightly reduces sensitivity to inhibition by AMP and Ca(2+) and activation by Mg(2+). Decreases binding to ALDOA.
    Mutagenesisi1 – 33Missing : No effect on kinetic properties but decreases binding to ALDOA.
    Mutagenesisi1 – 22Missing : No effect on kinetic properties and interaction with ALDOA.
    Mutagenesisi1 – 11Missing : No effect on kinetic properties and interaction with ALDOA.
    Mutagenesisi21 – 211K → E: Reduces sensitivity to AMP; when associated with M-178 and C-180. 1 Publication
    Mutagenesisi33 – 331Q → R: Causes conformational change of N-terminal residues and decreased sensitivity towards AMP with lack of conversion to the inactive T-state in the presence of AMP.
    Mutagenesisi70 – 701E → Q: Greatly reduces affinity towards Ca(2+) and slightly reduces affinity towards Mg(2+). 1 Publication
    Mutagenesisi178 – 1781T → M: Reduces sensitivity to AMP; when associated with E-21 and C-180. 1 Publication
    Mutagenesisi180 – 1801Q → C: Reduces sensitivity to AMP; when associated with E-21 and M-178. 1 Publication
    Mutagenesisi204 – 2085KKKGK → AAAGA or EEEGE: Almost completely abolishes nuclear localization. 1 Publication
    Mutagenesisi204 – 2041K → E: Minor reduction in nuclear localization.
    Mutagenesisi205 – 2051K → E: Minor reduction in nuclear localization.
    Mutagenesisi206 – 2061K → E: Greatly reduces nuclear lozalization.
    Mutagenesisi208 – 2081K → E: Significantly reduces nuclear localization.

    Organism-specific databases

    PharmGKBiPA28019.

    Polymorphism and mutation databases

    BioMutaiFBP2.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 339339Fructose-1,6-bisphosphatase isozyme 2PRO_0000200504Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei216 – 2161PhosphotyrosineBy similarity
    Modified residuei219 – 2191PhosphotyrosineBy similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiO00757.
    PaxDbiO00757.
    PeptideAtlasiO00757.
    PRIDEiO00757.

    PTM databases

    DEPODiO00757.
    iPTMnetiO00757.
    PhosphoSiteiO00757.
    SwissPalmiO00757.

    Expressioni

    Tissue specificityi

    Expressed in skeletal muscle (at protein level).1 Publication

    Gene expression databases

    BgeeiENSG00000130957.
    CleanExiHS_FBP2.
    GenevisibleiO00757. HS.

    Organism-specific databases

    HPAiHPA012513.

    Interactioni

    Subunit structurei

    Homotetramer. Interacts with ALDOA; the interaction blocks inhibition by physiological concentrations of AMP and reduces inhibition by Ca2+. Interacts with alpha-actinin and F-actin.3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    FBP1P094676EBI-719781,EBI-712740

    Protein-protein interaction databases

    BioGridi114317. 3 interactions.
    IntActiO00757. 20 interactions.
    MINTiMINT-1374932.
    STRINGi9606.ENSP00000364486.

    Structurei

    Secondary structure

    1
    339
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi14 – 2411Combined sources
    Helixi30 – 5021Combined sources
    Turni51 – 544Combined sources
    Turni58 – 614Combined sources
    Beta strandi70 – 723Combined sources
    Helixi74 – 8714Combined sources
    Turni88 – 903Combined sources
    Beta strandi92 – 976Combined sources
    Helixi108 – 1103Combined sources
    Beta strandi111 – 12212Combined sources
    Helixi124 – 1263Combined sources
    Turni127 – 1304Combined sources
    Beta strandi133 – 1419Combined sources
    Helixi150 – 1534Combined sources
    Helixi157 – 1593Combined sources
    Beta strandi161 – 18020Combined sources
    Beta strandi182 – 1887Combined sources
    Turni189 – 1924Combined sources
    Beta strandi193 – 2019Combined sources
    Beta strandi208 – 2114Combined sources
    Helixi214 – 2196Combined sources
    Helixi222 – 23211Combined sources
    Beta strandi235 – 2373Combined sources
    Helixi249 – 25911Combined sources
    Beta strandi262 – 2654Combined sources
    Beta strandi268 – 2703Combined sources
    Beta strandi275 – 2773Combined sources
    Turni278 – 2814Combined sources
    Helixi282 – 29110Combined sources
    Beta strandi295 – 2973Combined sources
    Beta strandi299 – 3024Combined sources
    Helixi303 – 3053Combined sources
    Beta strandi317 – 3215Combined sources
    Helixi322 – 33514Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3IFAX-ray1.93A/B/C/D2-339[»]
    3IFCX-ray1.97A/B/C/D2-339[»]
    4HE0X-ray2.69A2-339[»]
    4HE1X-ray2.23A2-339[»]
    4HE2X-ray1.60A2-339[»]
    5ET5X-ray1.67A2-339[»]
    5ET6X-ray1.84A/B/C/D2-339[»]
    5ET7X-ray2.99A/B/C/D2-339[»]
    ProteinModelPortaliO00757.
    SMRiO00757. Positions 9-337.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO00757.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni3 – 108Important for interaction with ALDOA
    Regioni213 – 2164Substrate binding
    Regioni245 – 2495Substrate binding

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi204 – 2085Nuclear localization signal1 Publication

    Sequence similaritiesi

    Belongs to the FBPase class 1 family.Curated

    Phylogenomic databases

    eggNOGiKOG1458. Eukaryota.
    COG0158. LUCA.
    GeneTreeiENSGT00390000015513.
    HOGENOMiHOG000191265.
    HOVERGENiHBG005627.
    InParanoidiO00757.
    KOiK03841.
    OMAiWPKPIRA.
    OrthoDBiEOG091G0AZP.
    PhylomeDBiO00757.
    TreeFamiTF314824.

    Family and domain databases

    CDDicd00354. FBPase. 1 hit.
    HAMAPiMF_01855. FBPase_class1. 1 hit.
    InterProiIPR000146. FBPase_class-1.
    IPR033391. FBPase_N.
    IPR028343. FBPtase.
    IPR020548. Fructose_bisphosphatase_AS.
    [Graphical view]
    PANTHERiPTHR11556. PTHR11556. 1 hit.
    PfamiPF00316. FBPase. 1 hit.
    [Graphical view]
    PIRSFiPIRSF500210. FBPtase. 1 hit.
    PIRSF000904. FBPtase_SBPase. 1 hit.
    PRINTSiPR00115. F16BPHPHTASE.
    PROSITEiPS00124. FBPASE. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O00757-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MTDRSPFETD MLTLTRYVME KGRQAKGTGE LTQLLNSMLT AIKAISSAVR
    60 70 80 90 100
    KAGLAHLYGI AGSVNVTGDE VKKLDVLSNS LVINMVQSSY STCVLVSEEN
    110 120 130 140 150
    KDAIITAKEK RGKYVVCFDP LDGSSNIDCL ASIGTIFAIY RKTSEDEPSE
    160 170 180 190 200
    KDALQCGRNI VAAGYALYGS ATLVALSTGQ GVDLFMLDPA LGEFVLVEKD
    210 220 230 240 250
    VKIKKKGKIY SLNEGYAKYF DAATTEYVQK KKFPEDGSAP YGARYVGSMV
    260 270 280 290 300
    ADVHRTLVYG GIFLYPANQK SPKGKLRLLY ECNPVAYIIE QAGGLATTGT
    310 320 330
    QPVLDVKPEA IHQRVPLILG SPEDVQEYLT CVQKNQAGS
    Length:339
    Mass (Da):36,743
    Last modified:September 27, 2005 - v2
    Checksum:i196B06D744710BC4
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti86 – 861V → L.2 Publications
    Corresponds to variant rs573212 [ dbSNP | Ensembl ].
    VAR_024448

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    Y10812 mRNA. Translation: CAA71772.1.
    CR536483 mRNA. Translation: CAG38722.1.
    AL161728 Genomic DNA. Translation: CAH72694.1.
    BC113632 mRNA. Translation: AAI13633.1.
    BC117477 mRNA. Translation: AAI17478.1.
    CCDSiCCDS6711.1.
    RefSeqiNP_003828.2. NM_003837.3.
    UniGeneiHs.61255.

    Genome annotation databases

    EnsembliENST00000375337; ENSP00000364486; ENSG00000130957.
    GeneIDi8789.
    KEGGihsa:8789.
    UCSCiuc004auv.5. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    Y10812 mRNA. Translation: CAA71772.1.
    CR536483 mRNA. Translation: CAG38722.1.
    AL161728 Genomic DNA. Translation: CAH72694.1.
    BC113632 mRNA. Translation: AAI13633.1.
    BC117477 mRNA. Translation: AAI17478.1.
    CCDSiCCDS6711.1.
    RefSeqiNP_003828.2. NM_003837.3.
    UniGeneiHs.61255.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3IFAX-ray1.93A/B/C/D2-339[»]
    3IFCX-ray1.97A/B/C/D2-339[»]
    4HE0X-ray2.69A2-339[»]
    4HE1X-ray2.23A2-339[»]
    4HE2X-ray1.60A2-339[»]
    5ET5X-ray1.67A2-339[»]
    5ET6X-ray1.84A/B/C/D2-339[»]
    5ET7X-ray2.99A/B/C/D2-339[»]
    ProteinModelPortaliO00757.
    SMRiO00757. Positions 9-337.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi114317. 3 interactions.
    IntActiO00757. 20 interactions.
    MINTiMINT-1374932.
    STRINGi9606.ENSP00000364486.

    PTM databases

    DEPODiO00757.
    iPTMnetiO00757.
    PhosphoSiteiO00757.
    SwissPalmiO00757.

    Polymorphism and mutation databases

    BioMutaiFBP2.

    Proteomic databases

    MaxQBiO00757.
    PaxDbiO00757.
    PeptideAtlasiO00757.
    PRIDEiO00757.

    Protocols and materials databases

    DNASUi8789.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000375337; ENSP00000364486; ENSG00000130957.
    GeneIDi8789.
    KEGGihsa:8789.
    UCSCiuc004auv.5. human.

    Organism-specific databases

    CTDi8789.
    GeneCardsiFBP2.
    HGNCiHGNC:3607. FBP2.
    HPAiHPA012513.
    MIMi603027. gene.
    neXtProtiNX_O00757.
    PharmGKBiPA28019.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1458. Eukaryota.
    COG0158. LUCA.
    GeneTreeiENSGT00390000015513.
    HOGENOMiHOG000191265.
    HOVERGENiHBG005627.
    InParanoidiO00757.
    KOiK03841.
    OMAiWPKPIRA.
    OrthoDBiEOG091G0AZP.
    PhylomeDBiO00757.
    TreeFamiTF314824.

    Enzyme and pathway databases

    UniPathwayiUPA00138.
    BioCyciMetaCyc:HS05462-MONOMER.
    ReactomeiR-HSA-70263. Gluconeogenesis.
    SABIO-RKO00757.

    Miscellaneous databases

    EvolutionaryTraceiO00757.
    GenomeRNAii8789.
    PROiO00757.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000130957.
    CleanExiHS_FBP2.
    GenevisibleiO00757. HS.

    Family and domain databases

    CDDicd00354. FBPase. 1 hit.
    HAMAPiMF_01855. FBPase_class1. 1 hit.
    InterProiIPR000146. FBPase_class-1.
    IPR033391. FBPase_N.
    IPR028343. FBPtase.
    IPR020548. Fructose_bisphosphatase_AS.
    [Graphical view]
    PANTHERiPTHR11556. PTHR11556. 1 hit.
    PfamiPF00316. FBPase. 1 hit.
    [Graphical view]
    PIRSFiPIRSF500210. FBPtase. 1 hit.
    PIRSF000904. FBPtase_SBPase. 1 hit.
    PRINTSiPR00115. F16BPHPHTASE.
    PROSITEiPS00124. FBPASE. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiF16P2_HUMAN
    AccessioniPrimary (citable) accession number: O00757
    Secondary accession number(s): Q17R39, Q6FI53
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: September 27, 2005
    Last modified: September 7, 2016
    This is version 145 of the entry and version 2 of the sequence. [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

    Miscellaneous

    Specific for the alpha-anomer of the substrate (PubMed:22120740). The Arg-33 mutant form has been shown to act on the beta-anomer (PubMed:24086250).2 Publications

    Keywords - Technical termi

    3D-structure, Allosteric enzyme, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 9
      Human chromosome 9: entries, gene names and cross-references to MIM
    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. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.