Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4

Gene

PFKFB4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at transcript 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.

Activity regulationi

The most important regulatory mechanism of these opposing activities is by phosphorylation and dephosphorylation of the enzyme.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei79Fructose 6-phosphateBy similarity1
Binding sitei103Fructose 6-phosphateBy similarity1
Active sitei129Sequence analysis1
Binding sitei131Fructose 6-phosphateBy similarity1
Binding sitei137Fructose 6-phosphateBy similarity1
Active sitei159Sequence analysis1
Binding sitei173Fructose 6-phosphateBy similarity1
Binding sitei194Fructose 6-phosphateBy similarity1
Binding sitei198Fructose 6-phosphateBy similarity1
Binding sitei256Fructose 2,6-bisphosphateBy similarity1
Active sitei257Tele-phosphohistidine intermediateBy similarity1
Binding sitei263Fructose 2,6-bisphosphateBy similarity1
Binding sitei269Fructose 2,6-bisphosphate; via amide nitrogenBy similarity1
Binding sitei306Fructose 2,6-bisphosphateBy 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 bindingi46 – 54ATPBy similarity9
Nucleotide bindingi168 – 173ATPBy similarity6
Nucleotide bindingi348 – 351ATPBy similarity4
Nucleotide bindingi392 – 396ATPBy similarity5

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

BioCyciMetaCyc:HS03750-MONOMER
BRENDAi2.7.1.105 2681
3.1.3.46 2681
ReactomeiR-HSA-70171 Glycolysis

Names & Taxonomyi

Protein namesi
Recommended name:
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4
Short name:
6PF-2-K/Fru-2,6-P2ase 4
Short name:
PFK/FBPase 4
Alternative name(s):
6PF-2-K/Fru-2,6-P2ase testis-type isozyme
Including the following 2 domains:
Fructose-2,6-bisphosphatase (EC:3.1.3.46)
Gene namesi
Name:PFKFB4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000114268.11
HGNCiHGNC:8875 PFKFB4
MIMi605320 gene
neXtProtiNX_Q16877

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Organism-specific databases

DisGeNETi5210
OpenTargetsiENSG00000114268
PharmGKBiPA33214

Chemistry databases

ChEMBLiCHEMBL3721311
DrugBankiDB04493 Fructose-6-Phosphate
DB04395 Phosphoaminophosphonic Acid-Adenylate Ester

Polymorphism and mutation databases

BioMutaiPFKFB4
DMDMi6226609

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001799701 – 4696-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4Add BLAST469

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei444Phosphothreonine; by PKCSequence analysis1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ16877
MaxQBiQ16877
PaxDbiQ16877
PeptideAtlasiQ16877
PRIDEiQ16877
ProteomicsDBi61116

PTM databases

DEPODiQ16877
iPTMnetiQ16877
PhosphoSitePlusiQ16877

Expressioni

Gene expression databases

BgeeiENSG00000114268 Expressed in 129 organ(s), highest expression level in blood
CleanExiHS_PFKFB4
ExpressionAtlasiQ16877 baseline and differential
GenevisibleiQ16877 HS

Organism-specific databases

HPAiHPA047719
HPA066058

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

BioGridi111231, 10 interactors
ComplexPortaliCPX-1996 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 complex
IntActiQ16877, 7 interactors
MINTiQ16877
STRINGi9606.ENSP00000232375

Chemistry databases

BindingDBiQ16877

Structurei

3D structure databases

ProteinModelPortaliQ16877
SMRiQ16877
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 2496-phosphofructo-2-kinaseAdd BLAST249
Regioni250 – 469Fructose-2,6-bisphosphataseAdd BLAST220

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG0234 Eukaryota
COG0406 LUCA
GeneTreeiENSGT00390000018751
HOGENOMiHOG000181112
HOVERGENiHBG005628
InParanoidiQ16877
KOiK19030
OMAiRIECYKN
OrthoDBiEOG091G0A43
PhylomeDBiQ16877
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 (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 6 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q16877-1) [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
MASPRELTQN PLKKIWMPYS NGRPALHACQ RGVCMTNCPT LIVMVGLPAR
60 70 80 90 100
GKTYISKKLT RYLNWIGVPT REFNVGQYRR DVVKTYKSFE FFLPDNEEGL
110 120 130 140 150
KIRKQCALAA LRDVRRFLSE EGGHVAVFDA TNTTRERRAT IFNFGEQNGY
160 170 180 190 200
KTFFVESICV DPEVIAANIV QVKLGSPDYV NRDSDEATED FMRRIECYEN
210 220 230 240 250
SYESLDEDLD RDLSYIKIMD VGQSYVVNRV ADHIQSRIVY YLMNIHVTPR
260 270 280 290 300
SIYLCRHGES ELNLKGRIGG DPGLSPRGRE FAKSLAQFIS DQNIKDLKVW
310 320 330 340 350
TSQMKRTIQT AEALGVPYEQ WKVLNEIDAG VCEEMTYEEI QDNYPLEFAL
360 370 380 390 400
RDQDKYRYRY PKGESYEDLV QRLEPVIMEL ERQENVLVIC HQAVMRCLLA
410 420 430 440 450
YFLDKAAEQL PYLKCPLHTV LKLTPVAYGC KVESIFLNVA AVNTHRDRPQ
460
NVDISRPPEE ALVTVPAHQ
Length:469
Mass (Da):54,040
Last modified:January 23, 2007 - v6
Checksum:i7E190C3C0A197D9F
GO
Isoform 2 (identifier: Q16877-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     330-364: Missing.

Show »
Length:434
Mass (Da):49,708
Checksum:i223B1A32CE970560
GO
Isoform 3 (identifier: Q16877-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-34: Missing.

Show »
Length:435
Mass (Da):50,203
Checksum:i814E51B938C76DA4
GO

Computationally mapped potential isoform sequencesi

There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q66S35Q66S35_HUMAN
6-phosphofructo-2-kinase/fructose-2...
PFKFB4
462Annotation score:
C9K0D8C9K0D8_HUMAN
6-phosphofructo-2-kinase/fructose-2...
PFKFB4
318Annotation score:
C9JX77C9JX77_HUMAN
6-phosphofructo-2-kinase/fructose-2...
PFKFB4
175Annotation score:
C9JJ23C9JJ23_HUMAN
6-phosphofructo-2-kinase/fructose-2...
PFKFB4
129Annotation score:
F8WC12F8WC12_HUMAN
6-phosphofructo-2-kinase/fructose-2...
PFKFB4
80Annotation score:
F8WDY1F8WDY1_HUMAN
6-phosphofructo-2-kinase/fructose-2...
PFKFB4
38Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_036075181N → K in a breast cancer sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0566211 – 34Missing in isoform 3. 2 PublicationsAdd BLAST34
Alternative sequenceiVSP_056530330 – 364Missing in isoform 2. 1 PublicationAdd BLAST35

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY756062 mRNA Translation: AAV28717.1
AY756064 mRNA Translation: AAV28719.1
D49818 mRNA Translation: BAA18921.1
AY714243 mRNA Translation: AAU14998.1
AF108765 mRNA Translation: AAD09427.1
AY786551 Genomic DNA Translation: AAV65753.1
AC134772 Genomic DNA No translation available.
CH471055 Genomic DNA Translation: EAW64890.1
BC010269 mRNA Translation: AAH10269.1
CCDSiCCDS2771.1 [Q16877-1]
CCDS82769.1 [Q16877-2]
PIRiJC5871
RefSeqiNP_001304063.1, NM_001317134.1
NP_001304064.1, NM_001317135.1
NP_001304065.1, NM_001317136.1
NP_001304066.1, NM_001317137.1 [Q16877-2]
NP_001304067.1, NM_001317138.1
NP_004558.1, NM_004567.3 [Q16877-1]
UniGeneiHs.476217

Genome annotation databases

EnsembliENST00000232375; ENSP00000232375; ENSG00000114268 [Q16877-1]
ENST00000383734; ENSP00000373240; ENSG00000114268 [Q16877-2]
GeneIDi5210
KEGGihsa:5210
UCSCiuc003ctv.4 human [Q16877-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY756062 mRNA Translation: AAV28717.1
AY756064 mRNA Translation: AAV28719.1
D49818 mRNA Translation: BAA18921.1
AY714243 mRNA Translation: AAU14998.1
AF108765 mRNA Translation: AAD09427.1
AY786551 Genomic DNA Translation: AAV65753.1
AC134772 Genomic DNA No translation available.
CH471055 Genomic DNA Translation: EAW64890.1
BC010269 mRNA Translation: AAH10269.1
CCDSiCCDS2771.1 [Q16877-1]
CCDS82769.1 [Q16877-2]
PIRiJC5871
RefSeqiNP_001304063.1, NM_001317134.1
NP_001304064.1, NM_001317135.1
NP_001304065.1, NM_001317136.1
NP_001304066.1, NM_001317137.1 [Q16877-2]
NP_001304067.1, NM_001317138.1
NP_004558.1, NM_004567.3 [Q16877-1]
UniGeneiHs.476217

3D structure databases

ProteinModelPortaliQ16877
SMRiQ16877
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111231, 10 interactors
ComplexPortaliCPX-1996 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 complex
IntActiQ16877, 7 interactors
MINTiQ16877
STRINGi9606.ENSP00000232375

Chemistry databases

BindingDBiQ16877
ChEMBLiCHEMBL3721311
DrugBankiDB04493 Fructose-6-Phosphate
DB04395 Phosphoaminophosphonic Acid-Adenylate Ester

PTM databases

DEPODiQ16877
iPTMnetiQ16877
PhosphoSitePlusiQ16877

Polymorphism and mutation databases

BioMutaiPFKFB4
DMDMi6226609

Proteomic databases

EPDiQ16877
MaxQBiQ16877
PaxDbiQ16877
PeptideAtlasiQ16877
PRIDEiQ16877
ProteomicsDBi61116

Protocols and materials databases

DNASUi5210
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000232375; ENSP00000232375; ENSG00000114268 [Q16877-1]
ENST00000383734; ENSP00000373240; ENSG00000114268 [Q16877-2]
GeneIDi5210
KEGGihsa:5210
UCSCiuc003ctv.4 human [Q16877-1]

Organism-specific databases

CTDi5210
DisGeNETi5210
EuPathDBiHostDB:ENSG00000114268.11
GeneCardsiPFKFB4
HGNCiHGNC:8875 PFKFB4
HPAiHPA047719
HPA066058
MIMi605320 gene
neXtProtiNX_Q16877
OpenTargetsiENSG00000114268
PharmGKBiPA33214
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0234 Eukaryota
COG0406 LUCA
GeneTreeiENSGT00390000018751
HOGENOMiHOG000181112
HOVERGENiHBG005628
InParanoidiQ16877
KOiK19030
OMAiRIECYKN
OrthoDBiEOG091G0A43
PhylomeDBiQ16877
TreeFamiTF313541

Enzyme and pathway databases

BioCyciMetaCyc:HS03750-MONOMER
BRENDAi2.7.1.105 2681
3.1.3.46 2681
ReactomeiR-HSA-70171 Glycolysis

Miscellaneous databases

ChiTaRSiPFKFB4 human
GeneWikiiPFKFB4
GenomeRNAii5210
PROiPR:Q16877
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000114268 Expressed in 129 organ(s), highest expression level in blood
CleanExiHS_PFKFB4
ExpressionAtlasiQ16877 baseline and differential
GenevisibleiQ16877 HS

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
ProtoNetiSearch...

Entry informationi

Entry nameiF264_HUMAN
AccessioniPrimary (citable) accession number: Q16877
Secondary accession number(s): Q5S3G5, Q5XLC2, Q64EX5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 23, 2007
Last modified: November 7, 2018
This is version 172 of the entry and version 6 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

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again