UniProtKB - O00757 (F16P2_HUMAN)
Protein
Fructose-1,6-bisphosphatase isozyme 2
Gene
FBP2
Organism
Homo sapiens (Human)
Status
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
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
Catalytic activityi
- EC:3.1.3.112 Publications
Cofactori
Mg2+2 PublicationsNote: Binds 3 Mg2+ ions per subunit.2 Publications
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. 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.
- KM=1.3 µM for fructose 1,6-bisphosphate2 Publications
- KM=2.6 µM for fructose 1,6-bisphosphate2 Publications
: gluconeogenesis Pathwayi
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 18 | AMP; via carbonyl oxygen1 Publication | 1 | |
Sitei | 33 | Important for the conversion from active R-state to inactive T-state in the presence of AMP | 1 | |
Metal bindingi | 69 | Magnesium 1 | 1 | |
Metal bindingi | 98 | Magnesium 1 | 1 | |
Metal bindingi | 98 | Magnesium 2 | 1 | |
Metal bindingi | 119 | Magnesium 2 | 1 | |
Metal bindingi | 119 | Magnesium 3 | 1 | |
Metal bindingi | 121 | Magnesium 2; via carbonyl oxygen | 1 | |
Metal bindingi | 122 | Magnesium 3 | 1 | |
Binding sitei | 122 | Substrate | 1 | |
Binding sitei | 141 | AMP1 Publication | 1 | |
Binding sitei | 265 | Substrate | 1 | |
Binding sitei | 275 | Substrate | 1 | |
Metal bindingi | 281 | Magnesium 3 | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 28 – 32 | AMP1 Publication | 5 | |
Nucleotide bindingi | 113 – 114 | AMP1 Publication | 2 |
GO - Molecular functioni
- fructose 1,6-bisphosphate 1-phosphatase activity Source: GO_Central
- identical protein binding Source: IntAct
- metal ion binding Source: UniProtKB-KW
GO - Biological processi
- fructose 1,6-bisphosphate metabolic process Source: GO_Central
- fructose 6-phosphate metabolic process Source: GO_Central
- fructose metabolic process Source: GO_Central
- gluconeogenesis Source: GO_Central
- sucrose biosynthetic process Source: GO_Central
Keywordsi
Molecular function | Allosteric enzyme, Hydrolase |
Biological process | Carbohydrate metabolism, Gluconeogenesis |
Ligand | Calcium, Magnesium, Metal-binding |
Enzyme and pathway databases
BioCyci | MetaCyc:HS05462-MONOMER |
PathwayCommonsi | O00757 |
Reactomei | R-HSA-70263, Gluconeogenesis |
SABIO-RKi | O00757 |
UniPathwayi | UPA00138 |
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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:3607, FBP2 |
MIMi | 603027, gene |
neXtProti | NX_O00757 |
VEuPathDBi | HostDB:ENSG00000130957.4 |
Subcellular locationi
Cytoplasm and Cytosol
Nucleus
Other locations
- Cell junction By similarity
- Z 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
Cytosol
- cytosol Source: HPA
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Nucleus
- nucleus Source: UniProtKB-SubCell
Plasma Membrane
- plasma membrane Source: HPA
Other locations
- cell junction Source: UniProtKB-SubCell
- cytoplasm Source: GO_Central
- Z disc Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cell junction, Cytoplasm, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 1 – 10 | Missing : Greatly reduces sensitivity to inhibition by AMP and Ca(2+) and activation by Mg(2+). Decreases binding to ALDOA. 1 Publication | 10 | |
Mutagenesisi | 1 – 7 | Missing : Greatly reduces sensitivity to inhibition by AMP and Ca(2+) and activation by Mg(2+). Decreases binding to ALDOA. | 7 | |
Mutagenesisi | 1 – 6 | Missing : Reduces sensitivity to inhibition by AMP and Ca(2+) and activation by Mg(2+). Decreases binding to ALDOA. | 6 | |
Mutagenesisi | 1 – 5 | Missing : Reduces sensitivity to inhibition by AMP and Ca(2+) and activation by Mg(2+). Decreases binding to ALDOA. | 5 | |
Mutagenesisi | 1 – 4 | Missing : Slightly reduces sensitivity to inhibition by AMP and Ca(2+) and activation by Mg(2+). Decreases binding to ALDOA. | 4 | |
Mutagenesisi | 1 – 3 | Missing : No effect on kinetic properties but decreases binding to ALDOA. | 3 | |
Mutagenesisi | 1 – 2 | Missing : No effect on kinetic properties and interaction with ALDOA. | 2 | |
Mutagenesisi | 1 | Missing : No effect on kinetic properties and interaction with ALDOA. | 1 | |
Mutagenesisi | 21 | K → E: Reduces sensitivity to AMP; when associated with M-178 and C-180. 1 Publication | 1 | |
Mutagenesisi | 33 | Q → 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 | |
Mutagenesisi | 70 | E → Q: Greatly reduces affinity towards Ca(2+) and slightly reduces affinity towards Mg(2+). 1 Publication | 1 | |
Mutagenesisi | 178 | T → M: Reduces sensitivity to AMP; when associated with E-21 and C-180. 1 Publication | 1 | |
Mutagenesisi | 180 | Q → C: Reduces sensitivity to AMP; when associated with E-21 and M-178. 1 Publication | 1 | |
Mutagenesisi | 204 – 208 | KKKGK → AAAGA or EEEGE: Almost completely abolishes nuclear localization. 1 Publication | 5 | |
Mutagenesisi | 204 | K → E: Minor reduction in nuclear localization. | 1 | |
Mutagenesisi | 205 | K → E: Minor reduction in nuclear localization. | 1 | |
Mutagenesisi | 206 | K → E: Greatly reduces nuclear lozalization. | 1 | |
Mutagenesisi | 208 | K → E: Significantly reduces nuclear localization. | 1 |
Organism-specific databases
DisGeNETi | 8789 |
OpenTargetsi | ENSG00000130957 |
PharmGKBi | PA28019 |
Miscellaneous databases
Pharosi | O00757, Tbio |
Genetic variation databases
BioMutai | FBP2 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000200504 | 1 – 339 | Fructose-1,6-bisphosphatase isozyme 2Add BLAST | 339 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 216 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 219 | PhosphotyrosineBy similarity | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | O00757 |
jPOSTi | O00757 |
MassIVEi | O00757 |
MaxQBi | O00757 |
PaxDbi | O00757 |
PeptideAtlasi | O00757 |
PRIDEi | O00757 |
ProteomicsDBi | 48020 |
PTM databases
DEPODi | FBP2 |
iPTMneti | O00757 |
PhosphoSitePlusi | O00757 |
SwissPalmi | O00757 |
Expressioni
Tissue specificityi
Expressed in skeletal muscle (at protein level).1 Publication
Gene expression databases
Bgeei | ENSG00000130957, Expressed in muscle of leg and 112 other tissues |
Genevisiblei | O00757, HS |
Organism-specific databases
HPAi | ENSG00000130957, Group enriched (brain, skeletal muscle, tongue) |
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 PublicationsBinary interactionsi
Hide detailsO00757
GO - Molecular functioni
- identical protein binding Source: IntAct
Protein-protein interaction databases
BioGRIDi | 114317, 21 interactors |
IntActi | O00757, 24 interactors |
MINTi | O00757 |
STRINGi | 9606.ENSP00000364486 |
Miscellaneous databases
RNActi | O00757, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | O00757 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | O00757 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 3 – 10 | Important for interaction with ALDOA1 Publication | 8 | |
Regioni | 213 – 216 | Substrate binding | 4 | |
Regioni | 245 – 249 | Substrate binding | 5 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 204 – 208 | Nuclear localization signal1 Publication | 5 |
Sequence similaritiesi
Belongs to the FBPase class 1 family.Curated
Phylogenomic databases
eggNOGi | KOG1458, Eukaryota |
GeneTreei | ENSGT00390000015513 |
HOGENOMi | CLU_039977_1_0_1 |
InParanoidi | O00757 |
OMAi | HEKSECY |
OrthoDBi | 1381522at2759 |
PhylomeDBi | O00757 |
TreeFami | TF314824 |
Family and domain databases
CDDi | cd00354, FBPase, 1 hit |
HAMAPi | MF_01855, FBPase_class1, 1 hit |
InterProi | View protein in InterPro IPR044015, FBPase_C_dom IPR000146, FBPase_class-1 IPR033391, FBPase_N IPR028343, FBPtase IPR020548, Fructose_bisphosphatase_AS |
PANTHERi | PTHR11556, PTHR11556, 1 hit |
Pfami | View protein in Pfam PF00316, FBPase, 1 hit PF18913, FBPase_C, 1 hit |
PIRSFi | PIRSF500210, FBPtase, 1 hit PIRSF000904, FBPtase_SBPase, 1 hit |
PRINTSi | PR00115, F16BPHPHTASE |
PROSITEi | View protein in PROSITE PS00124, FBPASE, 1 hit |
i Sequence
Sequence statusi: Complete.
O00757-1 [UniParc]FASTAAdd to basket
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
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_024448 | 86 | V → L2 PublicationsCorresponds to variant dbSNP:rs573212Ensembl. | 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 No translation available. BC113632 mRNA Translation: AAI13633.1 BC117477 mRNA Translation: AAI17478.1 |
CCDSi | CCDS6711.1 |
RefSeqi | NP_003828.2, NM_003837.3 |
Genome annotation databases
Ensembli | ENST00000375337; ENSP00000364486; ENSG00000130957 |
GeneIDi | 8789 |
KEGGi | hsa:8789 |
UCSCi | uc004auv.5, human |
Similar proteinsi
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 No translation available. BC113632 mRNA Translation: AAI13633.1 BC117477 mRNA Translation: AAI17478.1 |
CCDSi | CCDS6711.1 |
RefSeqi | NP_003828.2, NM_003837.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3IFA | X-ray | 1.93 | A/B/C/D | 2-339 | [»] | |
3IFC | X-ray | 1.97 | A/B/C/D | 2-339 | [»] | |
4HE0 | X-ray | 2.69 | A | 2-339 | [»] | |
4HE1 | X-ray | 2.23 | A | 2-339 | [»] | |
4HE2 | X-ray | 1.60 | A | 2-339 | [»] | |
5ET5 | X-ray | 1.67 | A | 2-339 | [»] | |
5ET6 | X-ray | 1.84 | A/B/C/D | 2-339 | [»] | |
5ET7 | X-ray | 2.99 | A/B/C/D | 2-339 | [»] | |
5ET8 | X-ray | 1.92 | A | 2-339 | [»] | |
5K54 | X-ray | 1.72 | A | 2-339 | [»] | |
5K55 | X-ray | 1.98 | A | 2-339 | [»] | |
5K56 | X-ray | 2.20 | A | 2-339 | [»] | |
5L0A | X-ray | 2.30 | A | 2-339 | [»] | |
5Q0C | X-ray | 2.40 | A/B/C/D/E/F/G/H | 1-339 | [»] | |
SMRi | O00757 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 114317, 21 interactors |
IntActi | O00757, 24 interactors |
MINTi | O00757 |
STRINGi | 9606.ENSP00000364486 |
PTM databases
DEPODi | FBP2 |
iPTMneti | O00757 |
PhosphoSitePlusi | O00757 |
SwissPalmi | O00757 |
Genetic variation databases
BioMutai | FBP2 |
Proteomic databases
EPDi | O00757 |
jPOSTi | O00757 |
MassIVEi | O00757 |
MaxQBi | O00757 |
PaxDbi | O00757 |
PeptideAtlasi | O00757 |
PRIDEi | O00757 |
ProteomicsDBi | 48020 |
Protocols and materials databases
Antibodypediai | 2920, 234 antibodies |
DNASUi | 8789 |
Genome annotation databases
Ensembli | ENST00000375337; ENSP00000364486; ENSG00000130957 |
GeneIDi | 8789 |
KEGGi | hsa:8789 |
UCSCi | uc004auv.5, human |
Organism-specific databases
CTDi | 8789 |
DisGeNETi | 8789 |
GeneCardsi | FBP2 |
HGNCi | HGNC:3607, FBP2 |
HPAi | ENSG00000130957, Group enriched (brain, skeletal muscle, tongue) |
MIMi | 603027, gene |
neXtProti | NX_O00757 |
OpenTargetsi | ENSG00000130957 |
PharmGKBi | PA28019 |
VEuPathDBi | HostDB:ENSG00000130957.4 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1458, Eukaryota |
GeneTreei | ENSGT00390000015513 |
HOGENOMi | CLU_039977_1_0_1 |
InParanoidi | O00757 |
OMAi | HEKSECY |
OrthoDBi | 1381522at2759 |
PhylomeDBi | O00757 |
TreeFami | TF314824 |
Enzyme and pathway databases
UniPathwayi | UPA00138 |
BioCyci | MetaCyc:HS05462-MONOMER |
PathwayCommonsi | O00757 |
Reactomei | R-HSA-70263, Gluconeogenesis |
SABIO-RKi | O00757 |
Miscellaneous databases
BioGRID-ORCSi | 8789, 19 hits in 984 CRISPR screens |
EvolutionaryTracei | O00757 |
GenomeRNAii | 8789 |
Pharosi | O00757, Tbio |
PROi | PR:O00757 |
RNActi | O00757, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000130957, Expressed in muscle of leg and 112 other tissues |
Genevisiblei | O00757, HS |
Family and domain databases
CDDi | cd00354, FBPase, 1 hit |
HAMAPi | MF_01855, FBPase_class1, 1 hit |
InterProi | View protein in InterPro IPR044015, FBPase_C_dom IPR000146, FBPase_class-1 IPR033391, FBPase_N IPR028343, FBPtase IPR020548, Fructose_bisphosphatase_AS |
PANTHERi | PTHR11556, PTHR11556, 1 hit |
Pfami | View protein in Pfam PF00316, FBPase, 1 hit PF18913, FBPase_C, 1 hit |
PIRSFi | PIRSF500210, FBPtase, 1 hit PIRSF000904, FBPtase_SBPase, 1 hit |
PRINTSi | PR00115, F16BPHPHTASE |
PROSITEi | View protein in PROSITE PS00124, FBPASE, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | F16P2_HUMAN | |
Accessioni | O00757Primary (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: | April 7, 2021 | |
This is version 176 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human chromosome 9
Human chromosome 9: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families