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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)DescriptionActionsGraphical viewLength
    Binding sitei18AMP; via carbonyl oxygen1 Publication1
    Sitei33Important for the conversion from active R-state to inactive T-state in the presence of AMP1
    Metal bindingi69Magnesium 11
    Metal bindingi98Magnesium 11
    Metal bindingi98Magnesium 21
    Metal bindingi119Magnesium 21
    Metal bindingi119Magnesium 31
    Metal bindingi121Magnesium 2; via carbonyl oxygen1
    Metal bindingi122Magnesium 31
    Binding sitei122Substrate1
    Binding sitei141AMP1 Publication1
    Binding sitei265Substrate1
    Binding sitei275Substrate1
    Metal bindingi281Magnesium 31

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi28 – 32AMP1 Publication5
    Nucleotide bindingi113 – 114AMP1 Publication2

    GO - Molecular functioni

    GO - Biological processi

    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.
    ZFISH: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: GO_Central
    • 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)DescriptionActionsGraphical viewLength
    Mutagenesisi1 – 10Missing : Greatly reduces sensitivity to inhibition by AMP and Ca(2+) and activation by Mg(2+). Decreases binding to ALDOA. 1 Publication10
    Mutagenesisi1 – 7Missing : Greatly reduces sensitivity to inhibition by AMP and Ca(2+) and activation by Mg(2+). Decreases binding to ALDOA. 7
    Mutagenesisi1 – 6Missing : Reduces sensitivity to inhibition by AMP and Ca(2+) and activation by Mg(2+). Decreases binding to ALDOA. 6
    Mutagenesisi1 – 5Missing : Reduces sensitivity to inhibition by AMP and Ca(2+) and activation by Mg(2+). Decreases binding to ALDOA. 5
    Mutagenesisi1 – 4Missing : Slightly reduces sensitivity to inhibition by AMP and Ca(2+) and activation by Mg(2+). Decreases binding to ALDOA. 4
    Mutagenesisi1 – 3Missing : No effect on kinetic properties but decreases binding to ALDOA. 3
    Mutagenesisi1 – 2Missing : No effect on kinetic properties and interaction with ALDOA. 2
    Mutagenesisi1Missing : No effect on kinetic properties and interaction with ALDOA. 1
    Mutagenesisi21K → E: Reduces sensitivity to AMP; when associated with M-178 and C-180. 1 Publication1
    Mutagenesisi33Q → 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. 1
    Mutagenesisi70E → Q: Greatly reduces affinity towards Ca(2+) and slightly reduces affinity towards Mg(2+). 1 Publication1
    Mutagenesisi178T → M: Reduces sensitivity to AMP; when associated with E-21 and C-180. 1 Publication1
    Mutagenesisi180Q → C: Reduces sensitivity to AMP; when associated with E-21 and M-178. 1 Publication1
    Mutagenesisi204 – 208KKKGK → AAAGA or EEEGE: Almost completely abolishes nuclear localization. 1 Publication5
    Mutagenesisi204K → E: Minor reduction in nuclear localization. 1
    Mutagenesisi205K → E: Minor reduction in nuclear localization. 1
    Mutagenesisi206K → E: Greatly reduces nuclear lozalization. 1
    Mutagenesisi208K → E: Significantly reduces nuclear localization. 1

    Organism-specific databases

    DisGeNETi8789.
    OpenTargetsiENSG00000130957.
    PharmGKBiPA28019.

    Polymorphism and mutation databases

    BioMutaiFBP2.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002005041 – 339Fructose-1,6-bisphosphatase isozyme 2Add BLAST339

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei216PhosphotyrosineBy similarity1
    Modified residuei219PhosphotyrosineBy similarity1

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiO00757.
    PaxDbiO00757.
    PeptideAtlasiO00757.
    PRIDEiO00757.

    PTM databases

    DEPODiO00757.
    iPTMnetiO00757.
    PhosphoSitePlusiO00757.
    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
    itself3EBI-719781,EBI-719781
    FBP1P0946710EBI-719781,EBI-712740

    Protein-protein interaction databases

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

    Structurei

    Secondary structure

    1339
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi14 – 24Combined sources11
    Helixi30 – 50Combined sources21
    Turni51 – 54Combined sources4
    Turni58 – 61Combined sources4
    Beta strandi70 – 72Combined sources3
    Helixi74 – 87Combined sources14
    Turni88 – 90Combined sources3
    Beta strandi92 – 97Combined sources6
    Helixi108 – 110Combined sources3
    Beta strandi111 – 122Combined sources12
    Helixi124 – 126Combined sources3
    Turni127 – 130Combined sources4
    Beta strandi133 – 141Combined sources9
    Helixi150 – 153Combined sources4
    Helixi157 – 159Combined sources3
    Beta strandi161 – 180Combined sources20
    Beta strandi182 – 188Combined sources7
    Turni189 – 192Combined sources4
    Beta strandi193 – 201Combined sources9
    Beta strandi208 – 211Combined sources4
    Helixi214 – 219Combined sources6
    Helixi222 – 232Combined sources11
    Beta strandi235 – 237Combined sources3
    Helixi249 – 259Combined sources11
    Beta strandi262 – 265Combined sources4
    Beta strandi268 – 270Combined sources3
    Beta strandi275 – 277Combined sources3
    Turni278 – 281Combined sources4
    Helixi282 – 291Combined sources10
    Beta strandi295 – 297Combined sources3
    Beta strandi299 – 302Combined sources4
    Helixi303 – 305Combined sources3
    Beta strandi317 – 321Combined sources5
    Helixi322 – 335Combined sources14

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB 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.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO00757.

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni3 – 10Important for interaction with ALDOA1 Publication8
    Regioni213 – 216Substrate binding4
    Regioni245 – 249Substrate binding5

    Motif

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Motifi204 – 208Nuclear localization signal1 Publication5

    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)DescriptionActionsGraphical viewLength
    Natural variantiVAR_02444886V → L.2 PublicationsCorresponds to variant rs573212dbSNPEnsembl.1

    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
    PDB 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.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

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

    PTM databases

    DEPODiO00757.
    iPTMnetiO00757.
    PhosphoSitePlusiO00757.
    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.
    DisGeNETi8789.
    GeneCardsiFBP2.
    HGNCiHGNC:3607. FBP2.
    HPAiHPA012513.
    MIMi603027. gene.
    neXtProtiNX_O00757.
    OpenTargetsiENSG00000130957.
    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.
    ZFISH: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: November 30, 2016
    This is version 148 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.