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Protein

6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 1

Gene

PFKFB1

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

Functioni

Synthesis and degradation of fructose 2,6-bisphosphate.

Catalytic activityi

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 regulationi

Phosphorylation at Ser-33 inhibits the kinase and activates the bisphosphatase.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei82Fructose 6-phosphateBy similarity1
Binding sitei105Fructose 6-phosphateBy similarity1
Active sitei131Sequence analysis1
Binding sitei133Fructose 6-phosphateBy similarity1
Binding sitei139Fructose 6-phosphateBy similarity1
Active sitei161Sequence analysis1
Binding sitei175Fructose 6-phosphateBy similarity1
Binding sitei196Fructose 6-phosphateBy similarity1
Binding sitei200Fructose 6-phosphateBy similarity1
Binding sitei258Fructose 2,6-bisphosphateBy similarity1
Active sitei259Tele-phosphohistidine intermediateBy similarity1
Binding sitei265Fructose 2,6-bisphosphateBy similarity1
Binding sitei271Fructose 2,6-bisphosphate; via amide nitrogenBy similarity1
Binding sitei308Fructose 2,6-bisphosphateBy similarity1
Active sitei328Proton donor/acceptorBy similarity1
Binding sitei339Fructose 2,6-bisphosphateBy similarity1
Binding sitei353Fructose 2,6-bisphosphateBy similarity1
Binding sitei357Fructose 2,6-bisphosphateBy similarity1
Binding sitei368Fructose 2,6-bisphosphateBy similarity1
Sitei393Transition state stabilizerBy similarity1
Binding sitei394Fructose 2,6-bisphosphateBy similarity1
Binding sitei398Fructose 2,6-bisphosphateBy similarity1
Binding sitei430ATP1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi49 – 57ATP1 Publication9
Nucleotide bindingi170 – 175ATP1 Publication6
Nucleotide bindingi350 – 353ATPBy similarity4
Nucleotide bindingi394 – 398ATPBy similarity5

GO - Molecular functioni

  • 6-phosphofructo-2-kinase activity Source: UniProtKB
  • ATP binding Source: UniProtKB-KW
  • fructose-2,6-bisphosphate 2-phosphatase activity Source: UniProtKB
  • fructose-6-phosphate binding Source: Ensembl
  • identical protein binding Source: IntAct

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS08310-MONOMER.
ZFISH:HS08310-MONOMER.
BRENDAi2.7.1.105. 2681.
3.1.3.46. 2681.
ReactomeiR-HSA-163358. PKA-mediated phosphorylation of key metabolic factors.
R-HSA-163767. PP2A-mediated dephosphorylation of key metabolic factors.
R-HSA-70171. Glycolysis.
R-HSA-70263. Gluconeogenesis.
SABIO-RKP16118.

Names & Taxonomyi

Protein namesi
Recommended 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:
Fructose-2,6-bisphosphatase (EC:3.1.3.46)
Gene namesi
Name:PFKFB1
Synonyms:F6PK, PFRX
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:8872. PFKFB1.

Subcellular locationi

GO - Cellular componenti

  • 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase complex Source: UniProtKB
  • cytosol Source: Reactome
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

DisGeNETi5207.
OpenTargetsiENSG00000158571.
PharmGKBiPA33211.

Chemistry databases

ChEMBLiCHEMBL3421524.

Polymorphism and mutation databases

DMDMi2507178.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001799602 – 4716-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 1Add BLAST470

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineBy similarity1
Modified residuei33Phosphoserine; by PKABy similarity1
Modified residuei141PhosphoserineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiP16118.
PeptideAtlasiP16118.
PRIDEiP16118.

PTM databases

DEPODiP16118.
iPTMnetiP16118.
PhosphoSitePlusiP16118.

Expressioni

Tissue specificityi

Liver.

Gene expression databases

BgeeiENSG00000158571.
CleanExiHS_PFKFB1.
ExpressionAtlasiP16118. baseline and differential.
GenevisibleiP16118. HS.

Interactioni

Subunit structurei

Homodimer.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
itself4EBI-709807,EBI-709807
GCKP355572EBI-709807,EBI-709928

GO - Molecular functioni

  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi111228. 7 interactors.
IntActiP16118. 5 interactors.
MINTiMINT-6772805.
STRINGi9606.ENSP00000364145.

Chemistry databases

BindingDBiP16118.

Structurei

Secondary structure

1471
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi43 – 48Combined sources6
Helixi55 – 68Combined sources14
Beta strandi73 – 77Combined sources5
Helixi78 – 83Combined sources6
Helixi91 – 94Combined sources4
Helixi99 – 121Combined sources23
Beta strandi126 – 132Combined sources7
Helixi137 – 150Combined sources14
Beta strandi153 – 160Combined sources8
Helixi164 – 175Combined sources12
Helixi187 – 201Combined sources15
Turni209 – 214Combined sources6
Beta strandi217 – 221Combined sources5
Turni222 – 225Combined sources4
Beta strandi226 – 230Combined sources5
Helixi235 – 244Combined sources10
Beta strandi254 – 258Combined sources5
Helixi263 – 266Combined sources4
Helixi278 – 293Combined sources16
Beta strandi300 – 303Combined sources4
Helixi307 – 314Combined sources8
Helixi324 – 326Combined sources3
Helixi332 – 334Combined sources3
Helixi339 – 345Combined sources7
Helixi347 – 355Combined sources9
Turni357 – 359Combined sources3
Helixi368 – 384Combined sources17
Beta strandi386 – 392Combined sources7
Helixi394 – 405Combined sources12
Turni409 – 411Combined sources3
Helixi412 – 414Combined sources3
Beta strandi421 – 427Combined sources7
Beta strandi429 – 438Combined sources10
Helixi460 – 464Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1K6MX-ray2.40A/B40-471[»]
ProteinModelPortaliP16118.
SMRiP16118.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP16118.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 2506-phosphofructo-2-kinaseAdd BLAST249
Regioni251 – 471Fructose-2,6-bisphosphataseAdd BLAST221

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG0234. Eukaryota.
COG0406. LUCA.
GeneTreeiENSGT00390000018751.
HOGENOMiHOG000181112.
HOVERGENiHBG005628.
InParanoidiP16118.
KOiK19028.
OMAiDYIDCDQ.
OrthoDBiEOG091G0A43.
PhylomeDBiP16118.
TreeFamiTF313541.

Family and domain databases

CDDicd07067. HP_PGM_like. 1 hit.
Gene3Di3.40.50.1240. 1 hit.
3.40.50.300. 1 hit.
InterProiIPR003094. 6Pfruct_kin.
IPR013079. 6Phosfructo_kin.
IPR013078. His_Pase_superF_clade-1.
IPR029033. His_PPase_superfam.
IPR027417. P-loop_NTPase.
IPR001345. PG/BPGM_mutase_AS.
[Graphical view]
PANTHERiPTHR10606. PTHR10606. 1 hit.
PfamiPF01591. 6PF2K. 1 hit.
PF00300. His_Phos_1. 1 hit.
[Graphical view]
PRINTSiPR00991. 6PFRUCTKNASE.
SMARTiSM00855. PGAM. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
SSF53254. SSF53254. 1 hit.
PROSITEiPS00175. PG_MUTASE. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P16118-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSPEMGELTQ TRLQKIWIPH SSGSSRLQRR RGSSIPQFTN SPTMVIMVGL
60 70 80 90 100
PARGKTYIST KLTRYLNWIG TPTKVFNLGQ YRREAVSYKN YEFFLPDNME
110 120 130 140 150
ALQIRKQCAL AALKDVHNYL SHEEGHVAVF DATNTTRERR SLILQFAKEH
160 170 180 190 200
GYKVFFIESI CNDPGIIAEN IRQVKLGSPD YIDCDREKVL EDFLKRIECY
210 220 230 240 250
EVNYQPLDEE LDSHLSYIKI FDVGTRYMVN RVQDHIQSRT VYYLMNIHVT
260 270 280 290 300
PRSIYLCRHG ESELNIRGRI GGDSGLSVRG KQYAYALANF IQSQGISSLK
310 320 330 340 350
VWTSHMKRTI QTAEALGVPY EQWKALNEID AGVCEEMTYE EIQEHYPEEF
360 370 380 390 400
ALRDQDKYRY RYPKGESYED LVQRLEPVIM ELERQENVLV ICHQAVMRCL
410 420 430 440 450
LAYFLDKSSD ELPYLKCPLH TVLKLTPVAY GCKVESIYLN VEAVNTHREK
460 470
PENVDITREP EEALDTVPAH Y
Length:471
Mass (Da):54,681
Last modified:November 1, 1997 - v3
Checksum:iC4FF081A295FB7D3
GO
Isoform 2 (identifier: P16118-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-73: MSPEMGELTQ...RYLNWIGTPT → MEEKTSRI

Show »
Length:406
Mass (Da):47,426
Checksum:i5D982E7DFBAC5CC1
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti305H → R in CAA36861 (PubMed:2163524).Curated1
Sequence conflicti359R → H in AAA35818 (PubMed:2837207).Curated1
Sequence conflicti397 – 398MR → HA in AAA35818 (PubMed:2837207).Curated2

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0547951 – 73MSPEM…IGTPT → MEEKTSRI in isoform 2. 1 PublicationAdd BLAST73

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X52638 mRNA. Translation: CAA36861.1.
AK314089 mRNA. Translation: BAG36785.1.
AK300724 mRNA. Translation: BAG62397.1.
AL049732, AL020991 Genomic DNA. Translation: CAI42048.1.
AL020991, AL049732 Genomic DNA. Translation: CAI43127.1.
BC096079 mRNA. Translation: AAH96079.1.
M19938 mRNA. Translation: AAA35818.1.
CCDSiCCDS14364.1. [P16118-1]
CCDS65273.1. [P16118-2]
PIRiS12732.
RefSeqiNP_001258733.1. NM_001271804.1.
NP_001258734.1. NM_001271805.1. [P16118-2]
NP_002616.2. NM_002625.3. [P16118-1]
UniGeneiHs.444304.

Genome annotation databases

EnsembliENST00000375006; ENSP00000364145; ENSG00000158571. [P16118-1]
ENST00000545676; ENSP00000444074; ENSG00000158571. [P16118-2]
GeneIDi5207.
KEGGihsa:5207.
UCSCiuc004dty.3. human. [P16118-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X52638 mRNA. Translation: CAA36861.1.
AK314089 mRNA. Translation: BAG36785.1.
AK300724 mRNA. Translation: BAG62397.1.
AL049732, AL020991 Genomic DNA. Translation: CAI42048.1.
AL020991, AL049732 Genomic DNA. Translation: CAI43127.1.
BC096079 mRNA. Translation: AAH96079.1.
M19938 mRNA. Translation: AAA35818.1.
CCDSiCCDS14364.1. [P16118-1]
CCDS65273.1. [P16118-2]
PIRiS12732.
RefSeqiNP_001258733.1. NM_001271804.1.
NP_001258734.1. NM_001271805.1. [P16118-2]
NP_002616.2. NM_002625.3. [P16118-1]
UniGeneiHs.444304.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1K6MX-ray2.40A/B40-471[»]
ProteinModelPortaliP16118.
SMRiP16118.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111228. 7 interactors.
IntActiP16118. 5 interactors.
MINTiMINT-6772805.
STRINGi9606.ENSP00000364145.

Chemistry databases

BindingDBiP16118.
ChEMBLiCHEMBL3421524.

PTM databases

DEPODiP16118.
iPTMnetiP16118.
PhosphoSitePlusiP16118.

Polymorphism and mutation databases

DMDMi2507178.

Proteomic databases

PaxDbiP16118.
PeptideAtlasiP16118.
PRIDEiP16118.

Protocols and materials databases

DNASUi5207.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000375006; ENSP00000364145; ENSG00000158571. [P16118-1]
ENST00000545676; ENSP00000444074; ENSG00000158571. [P16118-2]
GeneIDi5207.
KEGGihsa:5207.
UCSCiuc004dty.3. human. [P16118-1]

Organism-specific databases

CTDi5207.
DisGeNETi5207.
GeneCardsiPFKFB1.
HGNCiHGNC:8872. PFKFB1.
MIMi311790. gene.
neXtProtiNX_P16118.
OpenTargetsiENSG00000158571.
PharmGKBiPA33211.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0234. Eukaryota.
COG0406. LUCA.
GeneTreeiENSGT00390000018751.
HOGENOMiHOG000181112.
HOVERGENiHBG005628.
InParanoidiP16118.
KOiK19028.
OMAiDYIDCDQ.
OrthoDBiEOG091G0A43.
PhylomeDBiP16118.
TreeFamiTF313541.

Enzyme and pathway databases

BioCyciMetaCyc:HS08310-MONOMER.
ZFISH:HS08310-MONOMER.
BRENDAi2.7.1.105. 2681.
3.1.3.46. 2681.
ReactomeiR-HSA-163358. PKA-mediated phosphorylation of key metabolic factors.
R-HSA-163767. PP2A-mediated dephosphorylation of key metabolic factors.
R-HSA-70171. Glycolysis.
R-HSA-70263. Gluconeogenesis.
SABIO-RKP16118.

Miscellaneous databases

EvolutionaryTraceiP16118.
GenomeRNAii5207.
PROiP16118.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000158571.
CleanExiHS_PFKFB1.
ExpressionAtlasiP16118. baseline and differential.
GenevisibleiP16118. HS.

Family and domain databases

CDDicd07067. HP_PGM_like. 1 hit.
Gene3Di3.40.50.1240. 1 hit.
3.40.50.300. 1 hit.
InterProiIPR003094. 6Pfruct_kin.
IPR013079. 6Phosfructo_kin.
IPR013078. His_Pase_superF_clade-1.
IPR029033. His_PPase_superfam.
IPR027417. P-loop_NTPase.
IPR001345. PG/BPGM_mutase_AS.
[Graphical view]
PANTHERiPTHR10606. PTHR10606. 1 hit.
PfamiPF01591. 6PF2K. 1 hit.
PF00300. His_Phos_1. 1 hit.
[Graphical view]
PRINTSiPR00991. 6PFRUCTKNASE.
SMARTiSM00855. PGAM. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
SSF53254. SSF53254. 1 hit.
PROSITEiPS00175. PG_MUTASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiF261_HUMAN
AccessioniPrimary (citable) accession number: P16118
Secondary accession number(s): B2RA88
, B4DUN5, Q5JXS5, Q99951
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: November 1, 1997
Last modified: November 30, 2016
This is version 181 of the entry and version 3 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

Keywords - Technical termi

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

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.