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PFKFB4 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 [ Homo sapiens (human) ]

Gene ID: 5210, updated on 12-May-2016
Official Symbol
PFKFB4provided by HGNC
Official Full Name
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4provided by HGNC
Primary source
HGNC:HGNC:8875
See related
Ensembl:ENSG00000114268 HPRD:05613; MIM:605320; Vega:OTTHUMG00000133528
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary
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]
Orthologs
Location:
3p22-p21
Exon count:
18
Annotation release Status Assembly Chr Location
107 current GRCh38.p2 (GCF_000001405.28) 3 NC_000003.12 (48517684..48562774, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (48555117..48598607, complement)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene ATR interacting protein Neighboring gene three prime repair exonuclease 1 Neighboring gene shisa family member 5 Neighboring gene microRNA 6823 Neighboring gene collagen type VII alpha 1 Neighboring gene urocortin 2 Neighboring gene microRNA 711 Neighboring gene ubiquinol-cytochrome c reductase core protein I

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

NHGRI GWAS Catalog

Description
A genome-wide association study identifies a novel locus at 6q22.1 associated with ulcerative colitis.
NHGRI GWA Catalog
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
NHGRI GWA Catalog
  • AMPK signaling pathway, organism-specific biosystem (from KEGG)
    AMPK signaling pathway, organism-specific biosystemAMP-activated protein kinase (AMPK) is a serine threonine kinase that is highly conserved through evolution. AMPK system acts as a sensor of cellular energy status. It is activated by increases in th...
  • AMPK signaling pathway, conserved biosystem (from KEGG)
    AMPK signaling pathway, conserved biosystemAMP-activated protein kinase (AMPK) is a serine threonine kinase that is highly conserved through evolution. AMPK system acts as a sensor of cellular energy status. It is activated by increases in th...
  • Fructose and mannose metabolism, organism-specific biosystem (from KEGG)
    Fructose and mannose metabolism, organism-specific biosystem
    Fructose and mannose metabolism
  • Fructose and mannose metabolism, conserved biosystem (from KEGG)
    Fructose and mannose metabolism, conserved biosystem
    Fructose and mannose metabolism
  • Glucose metabolism, organism-specific biosystem (from REACTOME)
    Glucose metabolism, organism-specific biosystemGlucose is the major form in which dietary sugars are made available to cells of the human body. Its breakdown is a major source of energy for all cells, and is essential for the brain and red blood ...
  • Glycolysis, organism-specific biosystem (from REACTOME)
    Glycolysis, organism-specific biosystemThe reactions of glycolysis (e.g., van Wijk and van Solinge 2005) convert glucose 6-phosphate to pyruvate. The entire process is cytosolic. Glucose 6-phosphate is reversibly isomerized to form fructo...
  • Metabolism, organism-specific biosystem (from REACTOME)
    Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
  • Metabolism of carbohydrates, organism-specific biosystem (from REACTOME)
    Metabolism of carbohydrates, organism-specific biosystemThese pathways together are responsible for: 1) the extraction of energy and carbon skeletons for biosyntheses from dietary sugars and related molecules; 2) the short-term storage of glucose in the b...
  • fructose 2,6-bisphosphate biosynthesis, conserved biosystem (from BIOCYC)
    fructose 2,6-bisphosphate biosynthesis, conserved biosystemGeneral Background |FRAME: CPD-535 "Fructose-2,6-bisphosphate"| is a potent allosteric regulator with dual simultaneous functions. It is an activator of |FRAME: HS06881-MONOMER "phosphofructokinase"...
  • fructose 2,6-bisphosphate synthesis, organism-specific biosystem (from BIOCYC)
    fructose 2,6-bisphosphate synthesis, organism-specific biosystemGeneral Background : CPD-535 is a potent allosteric regulator with dual simultaneous functions. It is an activator of : HS06881-MONOMER "phosphofructokinase" and an inhibitor of : CPLX66-505 "fructo...
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
6-phosphofructo-2-kinase activity EXP
Inferred from Experiment
more info
PubMed 
6-phosphofructo-2-kinase activity NAS
Non-traceable Author Statement
more info
PubMed 
ATP binding IEA
Inferred from Electronic Annotation
more info
 
fructose-2,6-bisphosphate 2-phosphatase activity IEA
Inferred from Electronic Annotation
more info
 
Process Evidence Code Pubs
canonical glycolysis TAS
Traceable Author Statement
more info
 
carbohydrate phosphorylation IEA
Inferred from Electronic Annotation
more info
 
dephosphorylation IEA
Inferred from Electronic Annotation
more info
 
fructose 2,6-bisphosphate metabolic process IEA
Inferred from Electronic Annotation
more info
 
fructose metabolic process IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
cytosol TAS
Traceable Author Statement
more info
 
Preferred Names
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4
Names
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-4
6PF-2-K/Fru-2,6-P2ase 4
6PF-2-K/Fru-2,6-P2ase testis-type isozyme
PFK/FBPase 4
bifunctional enzyme with kinase and biphosphatase activities
NP_004558.1

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001317134.1NP_001304063.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 isoform a

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).
    Source sequence(s)
    AC134772, AY714243, BC010269, DB069657
    UniProtKB/Swiss-Prot
    Q16877
    Conserved Domains (3) summary
    cd07067
    Location:281466
    HP_PGM_like; Histidine phosphatase domain found in phosphoglycerate mutases and related proteins, mostly phosphatases; contains a His residue which is phosphorylated during the reaction
    pfam01591
    Location:64278
    6PF2K; 6-phosphofructo-2-kinase
    pfam13671
    Location:70225
    AAA_33; AAA domain
  2. NM_001317135.1NP_001304064.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 isoform c

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an alternate coding exon in the 5' end and uses an alternate in-frame splice junction compared to variant 1. The resulting isoform (c) has a shorter and distinct N-terminus and lacks an alternate internal segment compared to isoform a.
    Source sequence(s)
    AY707863, BC010269, DB069657
    UniProtKB/Swiss-Prot
    Q16877
    UniProtKB/TrEMBL
    Q66S35
    Conserved Domains (3) summary
    cd07067
    Location:252430
    HP_PGM_like; Histidine phosphatase domain found in phosphoglycerate mutases and related proteins, mostly phosphatases; contains a His residue which is phosphorylated during the reaction
    pfam01591
    Location:30249
    6PF2K; 6-phosphofructo-2-kinase
    pfam13671
    Location:41196
    AAA_33; AAA domain
  3. NM_001317136.1NP_001304065.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 isoform d

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) uses an alternate first exon in place of the first two exons compared to variant 1. The resulting isoform (d) has a shorter and distinct N-terminus compared to isoform a.
    Source sequence(s)
    AK298732, BC010269, DC423860
    UniProtKB/Swiss-Prot
    Q16877
    UniProtKB/TrEMBL
    B7Z5C3
    Conserved Domains (3) summary
    cd07067
    Location:241426
    HP_PGM_like; Histidine phosphatase domain found in phosphoglycerate mutases and related proteins, mostly phosphatases; contains a His residue which is phosphorylated during the reaction
    pfam01591
    Location:24238
    6PF2K; 6-phosphofructo-2-kinase
    pfam13671
    Location:30185
    AAA_33; AAA domain
  4. NM_001317137.1NP_001304066.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 isoform e

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) lacks an alternate coding exon in the 5' end and lacks an alternate in-frame exon compared to variant 1. The resulting isoform (e) has a shorter and distinct N-terminus and lacks an alternate internal segment compared to isoform a.
    Source sequence(s)
    AY756064, BC010269, DB069657
    UniProtKB/Swiss-Prot
    Q16877
    Conserved Domains (3) summary
    cd07067
    Location:252402
    HP_PGM_like; Histidine phosphatase domain found in phosphoglycerate mutases and related proteins, mostly phosphatases; contains a His residue which is phosphorylated during the reaction
    pfam01591
    Location:30249
    6PF2K; 6-phosphofructo-2-kinase
    pfam13671
    Location:41196
    AAA_33; AAA domain
  5. NM_001317138.1NP_001304067.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 isoform f

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) lacks an alternate exon in the 5' end and contains another alternate internal exon compared to variant 1. The resulting isoform (f) is shorter at the N-terminus compared to isoform a.
    Source sequence(s)
    AY756063, BC010269, DB069657
    UniProtKB/Swiss-Prot
    Q16877
    UniProtKB/TrEMBL
    Q5XLC3
    Conserved Domains (2) summary
    cd07067
    Location:61246
    HP_PGM_like; Histidine phosphatase domain found in phosphoglycerate mutases and related proteins, mostly phosphatases; contains a His residue which is phosphorylated during the reaction
    cl21455
    Location:158
    P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases
  6. NM_004567.3NP_004558.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 isoform b

    See identical proteins and their annotated locations for NP_004558.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate coding exon in the 5' end compared to variant 1. The resulting isoform (b) has a shorter and distinct N-terminus compared to isoform a.
    Source sequence(s)
    BC010269, DB069657
    Consensus CDS
    CCDS2771.1
    UniProtKB/Swiss-Prot
    Q16877
    Related
    ENSP00000232375, OTTHUMP00000164807, ENST00000232375, OTTHUMT00000257503
    Conserved Domains (3) summary
    cd07067
    Location:252437
    HP_PGM_like; Histidine phosphatase domain found in phosphoglycerate mutases and related proteins, mostly phosphatases; contains a His residue which is phosphorylated during the reaction
    pfam01591
    Location:30249
    6PF2K; 6-phosphofructo-2-kinase
    pfam13671
    Location:41196
    AAA_33; AAA domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 107 details...

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p2 Primary Assembly

Genomic

  1. NC_000003.12 Reference GRCh38.p2 Primary Assembly

    Range
    48517684..48562774 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011533829.1XP_011532131.1  

    Conserved Domains (3) summary
    cd07067
    Location:254439
    HP_PGM_like; Histidine phosphatase domain found in phosphoglycerate mutases and related proteins, mostly phosphatases; contains a His residue which is phosphorylated during the reaction
    pfam01591
    Location:37251
    6PF2K; 6-phosphofructo-2-kinase
    pfam13671
    Location:43198
    AAA_33; AAA domain
  2. XM_011533831.1XP_011532133.1  

    Conserved Domains (3) summary
    cd07067
    Location:241426
    HP_PGM_like; Histidine phosphatase domain found in phosphoglycerate mutases and related proteins, mostly phosphatases; contains a His residue which is phosphorylated during the reaction
    pfam01591
    Location:24238
    6PF2K; 6-phosphofructo-2-kinase
    pfam13671
    Location:30185
    AAA_33; AAA domain
  3. XM_005265231.3XP_005265288.1  

    Conserved Domains (2) summary
    cd07067
    Location:61246
    HP_PGM_like; Histidine phosphatase domain found in phosphoglycerate mutases and related proteins, mostly phosphatases; contains a His residue which is phosphorylated during the reaction
    cl21455
    Location:158
    P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases
  4. XM_005265230.1XP_005265287.1  

    Related
    ENSP00000373240, OTTHUMP00000210157, ENST00000383734, OTTHUMT00000344757
    Conserved Domains (3) summary
    cd07067
    Location:252402
    HP_PGM_like; Histidine phosphatase domain found in phosphoglycerate mutases and related proteins, mostly phosphatases; contains a His residue which is phosphorylated during the reaction
    pfam01591
    Location:30249
    6PF2K; 6-phosphofructo-2-kinase
    pfam13671
    Location:41196
    AAA_33; AAA domain
  5. XM_011533830.1XP_011532132.1  

    Conserved Domains (3) summary
    cd07067
    Location:254439
    HP_PGM_like; Histidine phosphatase domain found in phosphoglycerate mutases and related proteins, mostly phosphatases; contains a His residue which is phosphorylated during the reaction
    pfam01591
    Location:37251
    6PF2K; 6-phosphofructo-2-kinase
    pfam13671
    Location:43198
    AAA_33; AAA domain

Alternate CHM1_1.1

Genomic

  1. NC_018914.2 Alternate CHM1_1.1

    Range
    48507387..48546534 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)