PFKFB4

Protein identityUniProt · HPA

UniProt accession

Q16877

Gene

PFKFB4

Ensembl

ENSG00000114268

Chromosome

3

Canonical length

469 aa

Protein class

Enzymes, Metabolic proteins, Predicted intracellular proteins

Subcellular location

Nucleoli

Quaternary structure

Homodimer

OverviewNCBI Gene

The protein encoded by this gene is one of four bifunctional kinase/phosphatases that regulate the concentration of the glycolytic byproduct fructose-2,6-bisphosphate (F2,6BP). The encoded protein is highly expressed in cancer cells and is induced by hypoxia. This protein is essential to the survival of cancer cells under conditions of hypoxia, because it increases the amount of F2,6BP and ATP at a time when the cell cannot produce much of them. This finding suggests that this protein may be a good target for disruption in cancer cells, hopefully imperiling their survival. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

Canonical amino-acid sequenceUniProt

469 residues, UniProt reviewed canonical sequence.

>Q16877|PFKFB4
     1  MASPRELTQN PLKKIWMPYS NGRPALHACQ RGVCMTNCPT LIVMVGLPAR GKTYISKKLT
    61  RYLNWIGVPT REFNVGQYRR DVVKTYKSFE FFLPDNEEGL KIRKQCALAA LRDVRRFLSE
   121  EGGHVAVFDA TNTTRERRAT IFNFGEQNGY KTFFVESICV DPEVIAANIV QVKLGSPDYV
   181  NRDSDEATED FMRRIECYEN SYESLDEDLD RDLSYIKIMD VGQSYVVNRV ADHIQSRIVY
   241  YLMNIHVTPR SIYLCRHGES ELNLKGRIGG DPGLSPRGRE FAKSLAQFIS DQNIKDLKVW
   301  TSQMKRTIQT AEALGVPYEQ WKVLNEIDAG VCEEMTYEEI QDNYPLEFAL RDQDKYRYRY
   361  PKGESYEDLV QRLEPVIMEL ERQENVLVIC HQAVMRCLLA YFLDKAAEQL PYLKCPLHTV
   421  LKLTPVAYGC KVESIFLNVA AVNTHRDRPQ NVDISRPPEE ALVTVPAHQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PFKFB4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.25

Highest tissue expression

24 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.96

gnomAD pLI

0

gnomAD missense Z

1.36

DepMap mean gene effect

-0.23

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• fructose 2,6-bisphosphate metabolic process
• fructose metabolic process
• gluconeogenesis
• glycolytic process

Molecular functions

• 6-phosphofructo-2-kinase activity
• ATP binding
• fructose-2,6-bisphosphate 2-phosphatase activity

Cellular components

• 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase complex
• cytosol

Protein domainsUniProt · Pfam · InterPro

• Phosphoglycerate/bisphosphoglycerate mutase, active site
• Fructose-2,6-bisphosphatase
• Histidine phosphatase superfamily, clade-1
• 6-phosphofructo-2-kinase
• P-loop containing nucleoside triphosphate hydrolase
• Histidine phosphatase superfamily
• Histidine phosphatase superfamily (branch 1)
• 6-phosphofructo-2-kinase

KeywordsUniProt

• ATP-binding
• Hydrolase
• Kinase
• Multifunctional enzyme
• Nucleotide-binding
• Phosphoprotein
• Transferase

InteractionsUniProt · HPA

Protein binding partners of PFKFB4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• PFKFB1
• YWHAZ