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P07953 (F261_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 156. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 1

Short name=6PF-2-K/Fru-2,6-P2ase 1
Short name=PFK/FBPase 1
Alternative name(s):
6PF-2-K/Fru-2,6-P2ase liver isozyme

Including the following 2 domains:

  1. 6-phosphofructo-2-kinase
    EC=2.7.1.105
  2. Fructose-2,6-bisphosphatase
    EC=3.1.3.46
Gene names
Name:Pfkfb1
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length471 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Synthesis and degradation of fructose 2,6-bisphosphate.

Catalytic activity

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

ATP + D-fructose 6-phosphate = ADP + beta-D-fructose 2,6-bisphosphate.

Enzyme regulation

Phosphorylation at Ser-33 inhibits the kinase and activates the bisphosphatase. Ref.11

Subunit structure

Homodimer.

Tissue specificity

Liver.

Sequence similarities

In the C-terminal section; belongs to the phosphoglycerate mutase family.

Ontologies

Keywords
   Coding sequence diversityAlternative splicing
   LigandATP-binding
Nucleotide-binding
   Molecular functionHydrolase
Kinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Multifunctional enzyme
Reference proteome
Gene Ontology (GO)
   Biological_processcarbohydrate phosphorylation

Inferred from direct assay PubMed 7619077. Source: RGD

dephosphorylation

Inferred from direct assay PubMed 7619077. Source: GOC

fructose 2,6-bisphosphate metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

fructose metabolic process

Inferred from electronic annotation. Source: InterPro

organ regeneration

Inferred from expression pattern PubMed 1315037. Source: RGD

positive regulation of glucokinase activity

Inferred from mutant phenotype PubMed 15047617. Source: RGD

response to cAMP

Inferred from expression pattern PubMed 7593243. Source: RGD

response to glucagon

Inferred from expression pattern PubMed 7593243. Source: RGD

response to glucocorticoid

Inferred from expression pattern PubMed 7593243PubMed 8131849. Source: RGD

response to insulin

Inferred from expression pattern PubMed 8131849. Source: RGD

response to starvation

Inferred from expression pattern PubMed 9705027. Source: RGD

   Cellular_component6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 1 complex

Inferred from sequence or structural similarity. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

   Molecular_function6-phosphofructo-2-kinase activity

Inferred from direct assay PubMed 7619077. Source: RGD

ATP binding

Inferred from direct assay PubMed 7619077. Source: RGD

fructose-2,6-bisphosphate 2-phosphatase activity

Inferred from sequence or structural similarity. Source: UniProtKB

fructose-6-phosphate binding

Inferred from direct assay PubMed 7619077. Source: RGD

identical protein binding

Inferred from physical interaction PubMed 11522786PubMed 22668829Ref.12. Source: IntAct

kinase binding

Inferred from physical interaction PubMed 11522786. Source: RGD

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself5EBI-709873,EBI-709873

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P07953-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P07953-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-33: MSREMGELTQTRLQKIWIPHSSSSSVLQRRRGS → MEEKASKRTA

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.8
Chain2 – 4714706-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 1
PRO_0000179962

Regions

Nucleotide binding49 – 579ATP By similarity
Nucleotide binding170 – 1756ATP By similarity
Nucleotide binding350 – 3534ATP
Nucleotide binding394 – 3985ATP
Region2 – 2502496-phosphofructo-2-kinase
Region251 – 471221Fructose-2,6-bisphosphatase

Sites

Active site1311 Potential
Active site1611 Potential
Active site2591Tele-phosphohistidine intermediate Ref.13
Active site3281Proton donor/acceptor Ref.13
Active site3931Proton donor/acceptor Ref.13
Binding site821Fructose 6-phosphate By similarity
Binding site1051Fructose 6-phosphate By similarity
Binding site1331Fructose 6-phosphate By similarity
Binding site1391Fructose 6-phosphate By similarity
Binding site1751Fructose 6-phosphate By similarity
Binding site1961Fructose 6-phosphate By similarity
Binding site2001Fructose 6-phosphate By similarity
Binding site2581Fructose 2,6-bisphosphate By similarity
Binding site2651Fructose 2,6-bisphosphate By similarity
Binding site2711Fructose 2,6-bisphosphate; via amide nitrogen
Binding site3081Fructose 2,6-bisphosphate By similarity
Binding site3391Fructose 2,6-bisphosphate
Binding site3531Fructose 2,6-bisphosphate
Binding site3571Fructose 2,6-bisphosphate
Binding site3681Fructose 2,6-bisphosphate
Binding site3941Fructose 2,6-bisphosphate
Binding site3981Fructose 2,6-bisphosphate
Binding site4301ATP By similarity

Amino acid modifications

Modified residue21N-acetylserine Ref.5
Modified residue331Phosphoserine; by PKA Ref.11

Natural variations

Alternative sequence1 – 3333MSREM…RRRGS → MEEKASKRTA in isoform 2.
VSP_004674

Experimental info

Sequence conflict1351T → Y Ref.3
Sequence conflict1351T → Y Ref.4
Sequence conflict1351T → Y Ref.5
Sequence conflict1381E → F Ref.3
Sequence conflict2571Missing AA sequence Ref.7

Secondary structure

..................................... 471
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: E307AF13945E0FCD

FASTA47154,763
        10         20         30         40         50         60 
MSREMGELTQ TRLQKIWIPH SSSSSVLQRR RGSSIPQFTN SPTMVIMVGL PARGKTYIST 

        70         80         90        100        110        120 
KLTRYLNWIG TPTKVFNLGQ YRREAVSYRN YEFFRPDNTE AQLIRKQCAL AALKDVHKYL 

       130        140        150        160        170        180 
SREEGHVAVF DATNTTRERR SLILQFAKEH GYKVFFIESI CNDPEIIAEN IKQVKLGSPD 

       190        200        210        220        230        240 
YIDCDQEKVL EDFLKRIECY EINYQPLDEE LDSHLSYIKI FDVGTRYMVN RVQDHVQSRT 

       250        260        270        280        290        300 
AYYLMNIHVT PRSIYLCRHG ESELNLRGRI GGDSGLSARG KQYAYALANF IRSQGISSLK 

       310        320        330        340        350        360 
VWTSHMKRTI QTAEALGVPY EQWKALNEID AGVCEEMTYE EIQEHYPEEF ALRDQDKYRY 

       370        380        390        400        410        420 
RYPKGESYED LVQRLEPVIM ELERQENVLV ICHQAVMRCL LAYFLDKSSD ELPYLKCPLH 

       430        440        450        460        470 
TVLKLTPVAY GCRVESIYLN VEAVNTHRDK PENVDITREA EEALDTVPAH Y 

« Hide

Isoform 2 [UniParc].

Checksum: 3DCD00D54929917D
Show »

FASTA44852,070

References

[1]"Complete nucleotide sequence coding for rat liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase derived from a cDNA clone."
Darville M.I., Crepin K.M., Vandekerckhove J., van Damme J., Octave J.-N., Rider M.H., Marchand M.J., Hue L., Rousseau G.G.
FEBS Lett. 224:317-321(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1), PROTEIN SEQUENCE OF 16-29; 65-74; 90-105; 123-137; 189-195; 240-252; 259-266 AND 309-324 (ISOFORM 1).
Strain: Wistar.
Tissue: Liver.
[2]"Isolation of a cDNA clone for rat liver 6-phosphofructo 2-kinase/fructose 2,6-bisphosphatase."
Colosa A.D., Lively M.O., El-Maghrabi M.R., Pilkis S.J.
Biochem. Biophys. Res. Commun. 143:1092-1098(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1).
Strain: Sprague-Dawley.
[3]"Characterization of distinct mRNAs coding for putative isozymes of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase."
Crepin K.M., Darville M.I., Hue L., Rousseau G.G.
Eur. J. Biochem. 183:433-440(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
Strain: Wistar.
Tissue: Liver.
[4]"Induction of rat liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase mRNA by refeeding and insulin."
Colosia A.D., Marker A.J., Lange A.J., El-Maghrabi M.R., Granner D.K., Tauler A., Pilkis J., Pilkis S.J.
J. Biol. Chem. 263:18669-18677(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Liver.
[5]"Complete amino acid sequence of rat liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase."
Lively M.O., El-Maghrabi M.R., Pilkis J., D'Angelo G., Colosia A.D., Ciavola J.A., Fraser B.A., Pilkis S.J.
J. Biol. Chem. 263:839-849(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE (ISOFORM 1), ACETYLATION AT SER-2.
Tissue: Liver.
[6]"Cloning and expression in Escherichia coli of a rat hepatoma cell cDNA coding for 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase."
Crepin K.M., Darville M.I., Michel A., Hue L., Rousseau G.G.
Biochem. J. 264:151-160(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 2).
Strain: Wistar.
Tissue: Liver.
[7]"Active site sequence of hepatic fructose-2,6-bisphosphatase. Homology in primary structure with phosphoglycerate mutase."
Pilkis S.J., Lively M.O., El-Maghrabi M.R.
J. Biol. Chem. 262:12672-12675(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 220-267.
Tissue: Liver.
[8]"5' flanking sequence and structure of a gene encoding rat 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase."
Darville M.I., Crepin K.M., Hue L., Rousseau G.G.
Proc. Natl. Acad. Sci. U.S.A. 86:6543-6547(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-32 (ISOFORM 1), PROTEIN SEQUENCE OF 2-10 (ISOFORM 2).
[9]"Catalytic site of rat liver and bovine heart fructose-6-phosphate,2-kinase:fructose-2,6-bisphosphatase. Identification of fructose 6-phosphate binding site."
Kitamura K., Uyeda K., Hartman F.C., Kangawa K., Matsuo H.
J. Biol. Chem. 264:6344-6348(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 106-114, REGION.
[10]"Evolution of a bifunctional enzyme: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase."
Bazan J.F., Fletterick R.J., Pilkis S.J.
Proc. Natl. Acad. Sci. U.S.A. 86:9642-9646(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAINS.
[11]"Covalent control of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase: insights into autoregulation of a bifunctional enzyme."
Kurland I.J., Pilkis S.J.
Protein Sci. 4:1023-1037(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-33, ENZYME REGULATION.
[12]"Crystal structure of the rat liver fructose-2,6-bisphosphatase based on selenomethionine multiwavelength anomalous dispersion phases."
Lee Y.-H., Ogata C., Pflugrath J.W., Levitt D.G., Sarma R., Banaszak L.J., Pilkis S.J.
Biochemistry 35:6010-6019(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
Tissue: Liver.
[13]"Crystal structure of a trapped phosphoenzyme during a catalytic reaction."
Lee Y.-H., Olson T.W., Ogata C.M., Levitt D.G., Banaszak L.J., Lange A.J.
Nat. Struct. Biol. 4:615-618(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 251-441 IN COMPLEX WITH FRUCTOSE 6-PHOSPHATE, ACTIVE SITE.
[14]"Reaction mechanism of fructose-2,6-bisphosphatase suggested by the crystal structures of a pseudo-Michaelis complex and metabolite complexes."
Lee Y.-H., Olson T.W., McClard R.W., Witte J.F., McFarlan S.C., Banaszak L.J., Levitt D.G., Lange A.J.
Submitted (APR-2000) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 252-440 IN COMPLEXES WITH SUBSTRATE ANALOG AND WITH GTP.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y00702 mRNA. Translation: CAA68694.1.
X15579 mRNA. Translation: CAA33606.1.
X15580 mRNA. Translation: CAA33607.1.
M26215 Genomic DNA. Translation: AAA02888.2.
M26216 Genomic DNA. Translation: AAA02889.1.
J04197 mRNA. Translation: AAA79008.1.
M27886 Genomic DNA. Translation: AAA58780.1.
PIRKIRTFB. S11761.
RefSeqNP_036753.4. NM_012621.4. [P07953-1]
UniGeneRn.10115.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1C7ZX-ray2.60A/B252-441[»]
1C80X-ray2.20A/B252-441[»]
1C81X-ray2.50A252-441[»]
1FBTX-ray2.00A/B252-441[»]
1TIPX-ray2.20A/B252-441[»]
ProteinModelPortalP07953.
SMRP07953. Positions 7-471.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP07953. 2 interactions.
MINTMINT-8147404.

PTM databases

PhosphoSiteP07953.

Proteomic databases

PRIDEP07953.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000000178; ENSRNOP00000000178; ENSRNOG00000000165. [P07953-2]
ENSRNOT00000033656; ENSRNOP00000035212; ENSRNOG00000000165. [P07953-1]
GeneID24638.
KEGGrno:24638.

Organism-specific databases

CTD5207.
RGD3307. Pfkfb1.

Phylogenomic databases

eggNOGCOG0406.
GeneTreeENSGT00390000018751.
HOGENOMHOG000181112.
HOVERGENHBG005628.
InParanoidP07953.
KOK01103.
OMANIRGRIG.
OrthoDBEOG7M3J03.
PhylomeDBP07953.
TreeFamTF313541.

Enzyme and pathway databases

BRENDA3.1.3.46. 5301.
ReactomeREACT_205051. Metabolism.
REACT_206767. Disease.
SABIO-RKP07953.

Gene expression databases

GenevestigatorP07953.

Family and domain databases

Gene3D3.40.50.1240. 1 hit.
3.40.50.300. 1 hit.
InterProIPR003094. 6Pfruct_kin.
IPR013079. 6Phosfructo_kin.
IPR016260. Bifunct_6PFK/fruc_bisP_Ptase.
IPR013078. His_Pase_superF_clade-1.
IPR029033. His_PPase_superfam.
IPR027417. P-loop_NTPase.
IPR001345. PG/BPGM_mutase_AS.
[Graphical view]
PANTHERPTHR10606. PTHR10606. 1 hit.
PfamPF01591. 6PF2K. 1 hit.
PF00300. His_Phos_1. 1 hit.
[Graphical view]
PIRSFPIRSF000709. 6PFK_2-Ptase. 1 hit.
PRINTSPR00991. 6PFRUCTKNASE.
SMARTSM00855. PGAM. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 1 hit.
SSF53254. SSF53254. 1 hit.
PROSITEPS00175. PG_MUTASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP07953.
NextBio603924.
PROP07953.

Entry information

Entry nameF261_RAT
AccessionPrimary (citable) accession number: P07953
Secondary accession number(s): P16119
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 156 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references