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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

Keywordsi

Molecular functionHydrolase, Kinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS04690-MONOMER.
BRENDAi2.7.1.105. 2681.
3.1.3.46. 2681.
ReactomeiR-HSA-70171. Glycolysis.
SABIO-RKiO60825.
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

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 residuei472PhosphoserineBy similarity1
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. 21 interactors.
MINTiMINT-3000455.
STRINGi9606.ENSP00000356047.

Chemistry databases

BindingDBiO60825.

Structurei

Secondary structure

1505
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi39 – 44Combined sources6
Beta strandi47 – 50Combined sources4
Helixi51 – 64Combined sources14
Beta strandi69 – 73Combined sources5
Helixi74 – 82Combined sources9
Helixi88 – 91Combined sources4
Helixi96 – 119Combined sources24
Beta strandi123 – 129Combined sources7
Helixi134 – 147Combined sources14
Beta strandi150 – 157Combined sources8
Helixi161 – 174Combined sources14
Helixi186 – 200Combined sources15
Turni206 – 212Combined sources7
Beta strandi215 – 219Combined sources5
Turni220 – 223Combined sources4
Beta strandi224 – 228Combined sources5
Helixi233 – 242Combined sources10
Beta strandi252 – 256Combined sources5
Helixi261 – 265Combined sources5
Helixi276 – 292Combined sources17
Beta strandi298 – 301Combined sources4
Helixi305 – 312Combined sources8
Helixi322 – 324Combined sources3
Helixi330 – 332Combined sources3
Helixi337 – 343Combined sources7
Helixi345 – 353Combined sources9
Turni355 – 357Combined sources3
Helixi366 – 382Combined sources17
Beta strandi384 – 390Combined sources7
Helixi392 – 402Combined sources11
Turni407 – 409Combined sources3
Helixi410 – 412Combined sources3
Beta strandi419 – 426Combined sources8
Beta strandi429 – 436Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5HTKX-ray2.01A/B1-505[»]
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.
OMAiVKRPRLY.
OrthoDBiEOG091G0A43.
PhylomeDBiO60825.
TreeFamiTF313541.

Family and domain databases

CDDicd07067. HP_PGM_like. 1 hit.
Gene3Di3.40.50.1240. 1 hit.
InterProiView protein in InterPro
IPR003094. 6Pfruct_kin.
IPR013079. 6Phosfructo_kin.
IPR013078. His_Pase_superF_clade-1.
IPR029033. His_PPase_superfam.
IPR027417. P-loop_NTPase.
IPR001345. PG/BPGM_mutase_AS.
PANTHERiPTHR10606. PTHR10606. 1 hit.
PfamiView protein in Pfam
PF01591. 6PF2K. 1 hit.
PF00300. His_Phos_1. 1 hit.
PRINTSiPR00991. 6PFRUCTKNASE.
SMARTiView protein in SMART
SM00855. PGAM. 1 hit.
SUPFAMiSSF52540. SSF52540. 1 hit.
SSF53254. SSF53254. 1 hit.
PROSITEiView protein in PROSITE
PS00175. PG_MUTASE. 1 hit.

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

Similar proteinsi

Entry informationi

Entry nameiF262_HUMAN
AccessioniPrimary (citable) accession number: O60825
Secondary accession number(s): O60824
, Q5VVQ3, Q5VVQ4, Q9H3P1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: January 24, 2001
Last modified: August 30, 2017
This is version 171 of the entry and version 2 of the sequence. See 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 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families