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Protein

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

Gene

PFKFB2

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 results in the activation of the kinase activity.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei78Fructose 6-phosphateBy similarity1
Binding sitei102Fructose 6-phosphateBy similarity1
Active sitei128Sequence analysis1
Binding sitei130Fructose 6-phosphateBy similarity1
Binding sitei136Fructose 6-phosphateBy similarity1
Active sitei158Sequence analysis1
Binding sitei172Fructose 6-phosphateBy similarity1
Binding sitei193Fructose 6-phosphateBy similarity1
Binding sitei197Fructose 6-phosphateBy similarity1
Binding sitei256Fructose 2,6-bisphosphateBy similarity1
Sitei256Transition state stabilizerBy similarity1
Active sitei257Tele-phosphohistidine intermediateBy similarity1
Binding sitei263Fructose 2,6-bisphosphateBy similarity1
Sitei263Transition state stabilizerBy similarity1
Binding sitei269Fructose 2,6-bisphosphate; via amide nitrogenBy similarity1
Active sitei326Proton donor/acceptorBy similarity1
Binding sitei337Fructose 2,6-bisphosphateBy similarity1
Binding sitei351Fructose 2,6-bisphosphateBy similarity1
Binding sitei355Fructose 2,6-bisphosphateBy similarity1
Binding sitei366Fructose 2,6-bisphosphateBy similarity1
Sitei391Transition state stabilizerBy similarity1
Binding sitei392Fructose 2,6-bisphosphateBy similarity1
Binding sitei396Fructose 2,6-bisphosphateBy similarity1
Binding sitei428ATPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi45 – 53ATPBy similarity9
Nucleotide bindingi167 – 172ATPBy similarity6
Nucleotide bindingi348 – 351ATPBy similarity4
Nucleotide bindingi392 – 396ATPBy 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-EC
  • protein kinase binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS04690-MONOMER.
ZFISH:HS04690-MONOMER.
BRENDAi2.7.1.105. 2681.
3.1.3.46. 2681.
ReactomeiR-HSA-70171. Glycolysis.
SABIO-RKO60825.
SIGNORiO60825.

Names & Taxonomyi

Protein namesi
Recommended name:
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2
Short name:
6PF-2-K/Fru-2,6-P2ase 2
Short name:
PFK/FBPase 2
Alternative name(s):
6PF-2-K/Fru-2,6-P2ase heart-type isozyme
Including the following 2 domains:
Fructose-2,6-bisphosphatase (EC:3.1.3.46)
Gene namesi
Name:PFKFB2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:8873. PFKFB2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi466S → E: Constitutively active mutant that cannot be phosphorylated and further activated by AMPK. 1 Publication1

Organism-specific databases

DisGeNETi5208.
OpenTargetsiENSG00000123836.
PharmGKBiPA33212.

Chemistry databases

ChEMBLiCHEMBL3421525.

Polymorphism and mutation databases

BioMutaiPFKFB2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001799642 – 5056-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2Add BLAST504

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1
Modified residuei29Phosphoserine; by PKABy similarity1
Modified residuei466Phosphoserine; by AMPKCombined sources1 Publication1
Modified residuei468PhosphothreonineCombined sources1
Modified residuei475PhosphothreonineCombined sources1
Modified residuei483PhosphoserineCombined sources1
Modified residuei493PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylation by AMPK stimulates activity.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO60825.
MaxQBiO60825.
PaxDbiO60825.
PeptideAtlasiO60825.
PRIDEiO60825.

PTM databases

DEPODiO60825.
iPTMnetiO60825.
PhosphoSitePlusiO60825.

Expressioni

Tissue specificityi

Heart.

Gene expression databases

BgeeiENSG00000123836.
CleanExiHS_PFKFB2.
ExpressionAtlasiO60825. baseline and differential.
GenevisibleiO60825. HS.

Organism-specific databases

HPAiHPA049975.
HPA063575.

Interactioni

Subunit structurei

Homodimer.By similarity

GO - Molecular functioni

  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111229. 22 interactors.
IntActiO60825. 19 interactors.
MINTiMINT-3000455.
STRINGi9606.ENSP00000356047.

Chemistry databases

BindingDBiO60825.

Structurei

3D structure databases

ProteinModelPortaliO60825.
SMRiO60825.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 2486-phosphofructo-2-kinaseAdd BLAST247
Regioni249 – 505Fructose-2,6-bisphosphataseAdd BLAST257

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG0234. Eukaryota.
COG0406. LUCA.
GeneTreeiENSGT00390000018751.
HOGENOMiHOG000181112.
HOVERGENiHBG005628.
InParanoidiO60825.
KOiK19029.
OMAiDQNKFAY.
OrthoDBiEOG091G0A43.
PhylomeDBiO60825.
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: O60825-1) [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
MSGASSSEQN NNSYETKTPN LRMSEKKCSW ASYMTNSPTL IVMIGLPARG
60 70 80 90 100
KTYVSKKLTR YLNWIGVPTK VFNLGVYRRE AVKSYKSYDF FRHDNEEAMK
110 120 130 140 150
IRKQCALVAL EDVKAYLTEE NGQIAVFDAT NTTRERRDMI LNFAEQNSFK
160 170 180 190 200
VFFVESVCDD PDVIAANILE VKVSSPDYPE RNRENVMEDF LKRIECYKVT
210 220 230 240 250
YRPLDPDNYD KDLSFIKVIN VGQRFLVNRV QDYIQSKIVY YLMNIHVQPR
260 270 280 290 300
TIYLCRHGES EFNLLGKIGG DSGLSVRGKQ FAQALRKFLE EQEITDLKVW
310 320 330 340 350
TSQLKRTIQT AESLGVPYEQ WKILNEIDAG VCEEMTYAEI EKRYPEEFAL
360 370 380 390 400
RDQEKYLYRY PGGESYQDLV QRLEPVIMEL ERQGNVLVIS HQAVMRCLLA
410 420 430 440 450
YFLDKGADEL PYLRCPLHTI FKLTPVAYGC KVETIKLNVE AVNTHRDKPT
460 470 480 490 500
NNFPKNQTPV RMRRNSFTPL SSSNTIRRPR NYSVGSRPLK PLSPLRAQDM

QEGAD
Length:505
Mass (Da):58,477
Last modified:January 24, 2001 - v2
Checksum:i5CD6A933A7EBF604
GO
Isoform 2 (identifier: O60825-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     451-505: NNFPKNQTPV...RAQDMQEGAD → AAETTLAVRRRPSAASLMLPC

Show »
Length:471
Mass (Da):54,406
Checksum:i2B9C8957889F4D61
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti28Missing in CAA06605 (PubMed:9652401).Curated1
Sequence conflicti303 – 304QL → HV in CAA06606 (PubMed:9652401).Curated2
Sequence conflicti372R → L in CAA06606 (PubMed:9652401).Curated1
Sequence conflicti396R → H in CAA06606 (PubMed:9652401).Curated1
Sequence conflicti406G → D in CAA06606 (PubMed:9652401).Curated1
Sequence conflicti427A → T in CAA06606 (PubMed:9652401).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_004675451 – 505NNFPK…QEGAD → AAETTLAVRRRPSAASLMLP C in isoform 2. 3 PublicationsAdd BLAST55

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ005577 Genomic DNA. Translation: CAA06605.1.
AJ005578 mRNA. Translation: CAA06606.1.
AB044805 mRNA. Translation: BAB19681.1.
AF470623 mRNA. Translation: AAL99386.1.
AK292883 mRNA. Translation: BAF85572.1.
AL445493 Genomic DNA. Translation: CAH70777.1.
AL445493 Genomic DNA. Translation: CAH70778.1.
CH471100 Genomic DNA. Translation: EAW93508.1.
BC069350 mRNA. Translation: AAH69350.1.
BC069385 mRNA. Translation: AAH69385.1.
BC069583 mRNA. Translation: AAH69583.1.
BC069586 mRNA. Translation: AAH69586.1.
BC069600 mRNA. Translation: AAH69600.1.
BC075075 mRNA. Translation: AAH75075.1.
BC075076 mRNA. Translation: AAH75076.1.
BC112103 mRNA. Translation: AAI12104.1.
BC112105 mRNA. Translation: AAI12106.1.
CCDSiCCDS31003.1. [O60825-2]
CCDS31004.1. [O60825-1]
RefSeqiNP_001018063.1. NM_001018053.1. [O60825-2]
NP_006203.2. NM_006212.2. [O60825-1]
UniGeneiHs.282702.

Genome annotation databases

EnsembliENST00000367079; ENSP00000356046; ENSG00000123836. [O60825-2]
ENST00000367080; ENSP00000356047; ENSG00000123836. [O60825-1]
GeneIDi5208.
KEGGihsa:5208.
UCSCiuc001hfg.4. human. [O60825-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ005577 Genomic DNA. Translation: CAA06605.1.
AJ005578 mRNA. Translation: CAA06606.1.
AB044805 mRNA. Translation: BAB19681.1.
AF470623 mRNA. Translation: AAL99386.1.
AK292883 mRNA. Translation: BAF85572.1.
AL445493 Genomic DNA. Translation: CAH70777.1.
AL445493 Genomic DNA. Translation: CAH70778.1.
CH471100 Genomic DNA. Translation: EAW93508.1.
BC069350 mRNA. Translation: AAH69350.1.
BC069385 mRNA. Translation: AAH69385.1.
BC069583 mRNA. Translation: AAH69583.1.
BC069586 mRNA. Translation: AAH69586.1.
BC069600 mRNA. Translation: AAH69600.1.
BC075075 mRNA. Translation: AAH75075.1.
BC075076 mRNA. Translation: AAH75076.1.
BC112103 mRNA. Translation: AAI12104.1.
BC112105 mRNA. Translation: AAI12106.1.
CCDSiCCDS31003.1. [O60825-2]
CCDS31004.1. [O60825-1]
RefSeqiNP_001018063.1. NM_001018053.1. [O60825-2]
NP_006203.2. NM_006212.2. [O60825-1]
UniGeneiHs.282702.

3D structure databases

ProteinModelPortaliO60825.
SMRiO60825.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111229. 22 interactors.
IntActiO60825. 19 interactors.
MINTiMINT-3000455.
STRINGi9606.ENSP00000356047.

Chemistry databases

BindingDBiO60825.
ChEMBLiCHEMBL3421525.

PTM databases

DEPODiO60825.
iPTMnetiO60825.
PhosphoSitePlusiO60825.

Polymorphism and mutation databases

BioMutaiPFKFB2.

Proteomic databases

EPDiO60825.
MaxQBiO60825.
PaxDbiO60825.
PeptideAtlasiO60825.
PRIDEiO60825.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000367079; ENSP00000356046; ENSG00000123836. [O60825-2]
ENST00000367080; ENSP00000356047; ENSG00000123836. [O60825-1]
GeneIDi5208.
KEGGihsa:5208.
UCSCiuc001hfg.4. human. [O60825-1]

Organism-specific databases

CTDi5208.
DisGeNETi5208.
GeneCardsiPFKFB2.
HGNCiHGNC:8873. PFKFB2.
HPAiHPA049975.
HPA063575.
MIMi171835. gene.
neXtProtiNX_O60825.
OpenTargetsiENSG00000123836.
PharmGKBiPA33212.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0234. Eukaryota.
COG0406. LUCA.
GeneTreeiENSGT00390000018751.
HOGENOMiHOG000181112.
HOVERGENiHBG005628.
InParanoidiO60825.
KOiK19029.
OMAiDQNKFAY.
OrthoDBiEOG091G0A43.
PhylomeDBiO60825.
TreeFamiTF313541.

Enzyme and pathway databases

BioCyciMetaCyc:HS04690-MONOMER.
ZFISH:HS04690-MONOMER.
BRENDAi2.7.1.105. 2681.
3.1.3.46. 2681.
ReactomeiR-HSA-70171. Glycolysis.
SABIO-RKO60825.
SIGNORiO60825.

Miscellaneous databases

ChiTaRSiPFKFB2. human.
GeneWikiiPFKFB2.
GenomeRNAii5208.
PROiO60825.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000123836.
CleanExiHS_PFKFB2.
ExpressionAtlasiO60825. baseline and differential.
GenevisibleiO60825. 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 nameiF262_HUMAN
AccessioniPrimary (citable) accession number: O60825
Secondary accession number(s): O60824
, Q5VVQ3, Q5VVQ4, Q9H3P1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: January 24, 2001
Last modified: November 2, 2016
This is version 165 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

Keywords - Technical termi

Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: 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. 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.