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: Annotation score: 5 out of 5-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.

Enzyme 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

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS03750-MONOMER.
ZFISH: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

HGNCiHGNC:8875. PFKFB4.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

DisGeNETi5210.
OpenTargetsiENSG00000114268.
PharmGKBiPA33214.

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.

PTM databases

DEPODiQ16877.
iPTMnetiQ16877.
PhosphoSitePlusiQ16877.

Expressioni

Gene expression databases

BgeeiENSG00000114268.
CleanExiHS_PFKFB4.
ExpressionAtlasiQ16877. baseline and differential.
GenevisibleiQ16877. HS.

Organism-specific databases

HPAiHPA047719.
HPA066058.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

BioGridi111231. 5 interactors.
IntActiQ16877. 4 interactors.
MINTiMINT-8247435.
STRINGi9606.ENSP00000232375.

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.
OMAiDCSNDEA.
OrthoDBiEOG091G0A43.
PhylomeDBiQ16877.
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 (3)i

Sequence statusi: Complete.

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

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

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

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. 5 interactors.
IntActiQ16877. 4 interactors.
MINTiMINT-8247435.
STRINGi9606.ENSP00000232375.

PTM databases

DEPODiQ16877.
iPTMnetiQ16877.
PhosphoSitePlusiQ16877.

Polymorphism and mutation databases

BioMutaiPFKFB4.
DMDMi6226609.

Proteomic databases

EPDiQ16877.
MaxQBiQ16877.
PaxDbiQ16877.
PeptideAtlasiQ16877.
PRIDEiQ16877.

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.
GeneCardsiPFKFB4.
HGNCiHGNC:8875. PFKFB4.
HPAiHPA047719.
HPA066058.
MIMi605320. gene.
neXtProtiNX_Q16877.
OpenTargetsiENSG00000114268.
PharmGKBiPA33214.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiPFKFB4. human.
GeneWikiiPFKFB4.
GenomeRNAii5210.
PROiQ16877.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000114268.
CleanExiHS_PFKFB4.
ExpressionAtlasiQ16877. baseline and differential.
GenevisibleiQ16877. 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 nameiF264_HUMAN
AccessioniPrimary (citable) accession number: Q16877
Secondary accession number(s): Q5S3G5, Q5XLC2, Q64EX5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 160 of the entry and version 6 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 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.