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

Gene ID: 5210, updated on 23-Nov-2021

Summary

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 MIM:605320
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]
Expression
Broad expression in testis (RPKM 10.5), small intestine (RPKM 8.0) and 18 other tissues See more
Orthologs
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Genomic context

See PFKFB4 in Genome Data Viewer
Location:
3p21.31
Exon count:
20
Annotation release Status Assembly Chr Location
109.20211119 current GRCh38.p13 (GCF_000001405.39) 3 NC_000003.12 (48517684..48562383, complement)
105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (48555117..48598562, complement)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene ATRIP-TREX1 readthrough 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 chain Neighboring gene urocortin 2 Neighboring gene microRNA 711 Neighboring gene ubiquinol-cytochrome c reductase core protein 1 Neighboring gene small nucleolar RNA, H/ACA box 94

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
A genome-wide association study identifies a novel locus at 6q22.1 associated with ulcerative colitis.
GeneReviews: Not available
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
GeneReviews: Not available

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables 6-phosphofructo-2-kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
enables 6-phosphofructo-2-kinase activity NAS
Non-traceable Author Statement
more info
PubMed 
enables ATP binding IEA
Inferred from Electronic Annotation
more info
 
enables fructose-2,6-bisphosphate 2-phosphatase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
involved_in carbohydrate phosphorylation IEA
Inferred from Electronic Annotation
more info
 
involved_in dephosphorylation IEA
Inferred from Electronic Annotation
more info
 
involved_in fructose 2,6-bisphosphate metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
involved_in fructose metabolic process IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
 

General protein information

Preferred Names
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4
Names
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_001304063.1
NP_001304064.1
NP_001304065.1
NP_001304066.1
NP_001304067.1
NP_004558.1
XP_011532131.1
XP_016862103.1
XP_016862104.1
XP_016862105.1
XP_016862106.1
XP_024309363.1

NCBI Reference Sequences (RefSeq)

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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_001317134.2NP_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
    UniProtKB/Swiss-Prot
    Q16877
    Conserved Domains (3) summary
    pfam00300
    Location:281464
    His_Phos_1; Histidine phosphatase superfamily (branch 1)
    pfam01591
    Location:64278
    6PF2K; 6-phosphofructo-2-kinase
    pfam13671
    Location:70225
    AAA_33; AAA domain
  2. NM_001317135.2NP_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
    Consensus CDS
    CCDS82770.1
    UniProtKB/Swiss-Prot
    Q16877
    UniProtKB/TrEMBL
    Q66S35
    Related
    ENSP00000388394.1, ENST00000416568.5
    Conserved Domains (2) summary
    pfam01591
    Location:30249
    6PF2K; 6-phosphofructo-2-kinase
    pfam00300
    Location:252431
    His_Phos_1; Histidine phosphatase superfamily (branch 1)
  3. NM_001317136.2NP_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
    UniProtKB/Swiss-Prot
    Q16877
    UniProtKB/TrEMBL
    B7Z5C3
    Conserved Domains (3) summary
    pfam00300
    Location:241424
    His_Phos_1; Histidine phosphatase superfamily (branch 1)
    pfam01591
    Location:24238
    6PF2K; 6-phosphofructo-2-kinase
    pfam13671
    Location:30185
    AAA_33; AAA domain
  4. NM_001317137.2NP_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
    Consensus CDS
    CCDS82769.1
    UniProtKB/Swiss-Prot
    Q16877
    Related
    ENSP00000373240.2, ENST00000383734.6
    Conserved Domains (2) 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
  5. NM_001317138.2NP_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
    UniProtKB/Swiss-Prot
    Q16877
    UniProtKB/TrEMBL
    Q5XLC3
    Conserved Domains (2) summary
    pfam00300
    Location:61244
    His_Phos_1; Histidine phosphatase superfamily (branch 1)
    cl17190
    Location:158
    NK; Nucleoside/nucleotide kinase (NK) is a protein superfamily consisting of multiple families of enzymes that share structural similarity and are functionally related to the catalysis of the reversible phosphate group transfer from nucleoside triphosphates ...
  6. NM_004567.4NP_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
    ENSP00000232375.3, ENST00000232375.8
    Conserved Domains (2) summary
    pfam01591
    Location:30249
    6PF2K; 6-phosphofructo-2-kinase
    pfam00300
    Location:252438
    His_Phos_1; Histidine phosphatase superfamily (branch 1)

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20211119

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000003.12 Reference GRCh38.p13 Primary Assembly

    Range
    48517684..48562383 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011533829.2XP_011532131.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 isoform X2

    Conserved Domains (3) summary
    pfam00300
    Location:254437
    His_Phos_1; Histidine phosphatase superfamily (branch 1)
    pfam01591
    Location:37251
    6PF2K; 6-phosphofructo-2-kinase
    pfam13671
    Location:43198
    AAA_33; AAA domain
  2. XM_017006617.1XP_016862106.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 isoform X5

  3. XM_017006616.1XP_016862105.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 isoform X4

  4. XM_017006615.1XP_016862104.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 isoform X3

  5. XM_017006614.1XP_016862103.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 isoform X1

  6. XM_024453595.1XP_024309363.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 isoform X6

    Conserved Domains (2) summary
    pfam01591
    Location:1215
    6PF2K; 6-phosphofructo-2-kinase
    pfam00300
    Location:218404
    His_Phos_1; Histidine phosphatase superfamily (branch 1)
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