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PFKFB2 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 [ Homo sapiens (human) ]

Gene ID: 5208, updated on 3-Nov-2024

Summary

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Official Symbol
PFKFB2provided by HGNC
Official Full Name
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2provided by HGNC
Primary source
HGNC:HGNC:8873
See related
Ensembl:ENSG00000123836 MIM:171835; AllianceGenome:HGNC:8873
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
Also known as
PFK-2/FBPase-2
Summary
The protein encoded by this gene is involved in both the synthesis and degradation of fructose-2,6-bisphosphate, a regulatory molecule that controls glycolysis in eukaryotes. The encoded protein has a 6-phosphofructo-2-kinase activity that catalyzes the synthesis of fructose-2,6-bisphosphate, and a fructose-2,6-biphosphatase activity that catalyzes the degradation of fructose-2,6-bisphosphate. This protein regulates fructose-2,6-bisphosphate levels in the heart, while a related enzyme encoded by a different gene regulates fructose-2,6-bisphosphate levels in the liver and muscle. This enzyme functions as a homodimer. Two transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Expression
Broad expression in thyroid (RPKM 25.6), duodenum (RPKM 11.7) and 19 other tissues See more
Orthologs
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Genomic context

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See PFKFB2 in Genome Data Viewer
Location:
1q32.1
Exon count:
22
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (207034416..207081027)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (206299607..206346250)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (207226620..207254372)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene tRNA-Pro (anticodon TGG) 5-1 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr1:207192892-207194091 Neighboring gene chromosome 1 open reading frame 116 Neighboring gene small nucleolar RNA U13 Neighboring gene Sharpr-MPRA regulatory region 4428 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:207224117-207224687 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:207225911-207226550 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:207240869-207241100 Neighboring gene YOD1 deubiquitinase Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2439 Neighboring gene complement component 4 binding protein beta Neighboring gene uncharacterized LOC107985251 Neighboring gene complement component 4 binding protein alpha

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues 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

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Related articles in PubMed

  1. The stimulation of glycolysis by hypoxia in activated monocytes is mediated by AMP-activated protein kinase and inducible 6-phosphofructo-2-kinase. Marsin AS, et al. J Biol Chem, 2002 Aug 23. PMID 12065600
  2. A cis-eQTL in PFKFB2 is associated with diabetic nephropathy, adiposity and insulin secretion in American Indians. Muller YL, et al. Hum Mol Genet, 2015 May 15. PMID 25662186, Free PMC Article
  3. A fundamental trade-off in covalent switching and its circumvention by enzyme bifunctionality in glucose homeostasis. Dasgupta T, et al. J Biol Chem, 2014 May 9. PMID 24634222, Free PMC Article
  4. Upregulation of heart PFK-2/FBPase-2 isozyme in skeletal muscle after persistent contraction. Rovira J, et al. Pflugers Arch, 2012 Apr. PMID 22241065
  5. Expression, regulation and function of phosphofructo-kinase/fructose-biphosphatases (PFKFBs) in glucocorticoid-induced apoptosis of acute lymphoblastic leukemia cells. Carlet M, et al. BMC Cancer, 2010 Nov 23. PMID 21092265, Free PMC Article

See all (87) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. miR-21-5p inhibits the growth of brain glioma cells through regulating the glycolysis mediated by PFKFB2.
    Title: miR-21-5p inhibits the growth of brain glioma cells through regulating the glycolysis mediated by PFKFB2.
  2. PFKFB2 is a favorable prognostic biomarker for colorectal cancer by suppressing metastasis and tumor glycolysis.
    Title: PFKFB2 is a favorable prognostic biomarker for colorectal cancer by suppressing metastasis and tumor glycolysis.
  3. Knockdown circZNF131 Inhibits Cell Progression and Glycolysis in Gastric Cancer Through miR-186-5p/PFKFB2 Axis.
    Title: Knockdown circZNF131 Inhibits Cell Progression and Glycolysis in Gastric Cancer Through miR-186-5p/PFKFB2 Axis.
  4. PFKFB2 regulates glycolysis and proliferation in pancreatic cancer cells.
    Title: PFKFB2 regulates glycolysis and proliferation in pancreatic cancer cells.
  5. miR-613 served as a tumor suppressor by targeting PFKFB2, indicating that detecting miR-613 and modulation of miR-613 expression could be potential marker and clinical approach in gastric cancer patients
    Title: miR-613 inhibits Warburg effect in gastric cancer by targeting PFKFB2.
  6. This study aims to characterise the expression and phosphorylation of isozymes of the key glycolytic regulatory protein, 6-phosphofructokinase-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2), in urinary exosomes of subjects with pre-eclampsia .
    Title: Increased expression and phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoforms in urinary exosomes in pre-eclampsia.
  7. Lower PFKFB2 methylation levels was an independent factor of high relapse risk (Hazard Ratio = 3.2; CI95% = 1.19.5). PFKFB2 promoter methylation analysis has potential applicability to better stratify well-differentiated thyroid carcinomas (WDTC) patients according to the recurrence risk, independently of BRAF and TERT mutations.
    Title: PFKFB2 Promoter Hypomethylation as Recurrence Predictive Marker in Well-Differentiated Thyroid Carcinomas.
  8. these results indicate that RSK-mediated phosphorylation of PFKFB2 plays a key role in the metabolism and growth of BRAF-mutated melanomas.Significance: RSK promotes glycolytic metabolism and the growth of BRAF-mutated melanoma by driving phosphorylation of an important glycolytic enzyme
    Title: RSK Regulates PFK-2 Activity to Promote Metabolic Rewiring in Melanoma.
  9. UCA1/miR-182/PFKFB2 axis modulates chemokine CXCL14 secretion, glycolysis and invasion of glioma cells in glioblastoma-associated stromal cells .
    Title: Long non-coding RNA UCA1/miR-182/PFKFB2 axis modulates glioblastoma-associated stromal cells-mediated glycolysis and invasion of glioma cells.
  10. Crystal structure of human and cattle heart PFKFB2 and the inhibitory influence of citrate on substrate binding has been described.
    Title: Crystal structure of heart 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB2) and the inhibitory influence of citrate on substrate binding.
Submit: New GeneRIF Correction See all GeneRIFs (20)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC138308, MGC138310, DKFZp781D2217

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables 6-phosphofructo-2-kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables 6-phosphofructo-2-kinase activity IDA
Inferred from Direct Assay
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
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein kinase 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 fructose 2,6-bisphosphate metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in fructose metabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in glucose catabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in glycolytic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in lactate metabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of insulin secretion IEA
Inferred from Electronic Annotation
more info
  
involved_in response to glucose IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  

General protein information

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Preferred Names
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2
Names
6PF-2-K/Fru-2,6-P2ASE heart-type isozyme
6PF-2-K/Fru-2,6-P2ase 2
PFK/FBPase 2
PFKFB, cardiac
fructose-2,6-bisphosphatase, cardiac isozyme
NP_001018063.1
NP_006203.2
XP_005273219.1
XP_024303422.1
XP_024303423.1
XP_024303424.1
XP_024303425.1
XP_047278503.1
XP_047278504.1
XP_047278505.1
XP_054192998.1
XP_054192999.1
XP_054193000.1
XP_054193001.1
XP_054193002.1
XP_054193003.1
XP_054193004.1
XP_054193005.1

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_001018053.2 → NP_001018063.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 isoform b

    See identical proteins and their annotated locations for NP_001018063.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 3' UTR and coding region compared to variant 1. The resulting isoform (b) is shorter and has a distinct C-terminus compared to isoform a.
    Source sequence(s)
    AF470623, AL445493, BX510096
    Consensus CDS
    CCDS31003.1
    UniProtKB/Swiss-Prot
    O60825
    Related
    ENSP00000356046.2, ENST00000367079.3
    Conserved Domains (2) summary
    pfam00300
    Location:252 → 435
    His_Phos_1; Histidine phosphatase superfamily (branch 1)
    pfam01591
    Location:26 → 249
    6PF2K; 6-phosphofructo-2-kinase

  2. NM_006212.2 → NP_006203.2  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 isoform a

    See identical proteins and their annotated locations for NP_006203.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a).
    Source sequence(s)
    AL445493, BC069583, BX510096
    Consensus CDS
    CCDS31004.1
    UniProtKB/Swiss-Prot
    O60824, O60825, Q5VVQ3, Q5VVQ4, Q9H3P1
    Related
    ENSP00000356047.3, ENST00000367080.8
    Conserved Domains (2) summary
    pfam00300
    Location:252 → 435
    His_Phos_1; Histidine phosphatase superfamily (branch 1)
    pfam01591
    Location:26 → 249
    6PF2K; 6-phosphofructo-2-kinase

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    207034416..207081027
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047422548.1 → XP_047278504.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 isoform X1

    UniProtKB/Swiss-Prot
    O60824, O60825, Q5VVQ3, Q5VVQ4, Q9H3P1

  2. XM_047422547.1 → XP_047278503.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 isoform X1

    UniProtKB/Swiss-Prot
    O60824, O60825, Q5VVQ3, Q5VVQ4, Q9H3P1

  3. XM_024447657.2 → XP_024303425.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 isoform X3

    Conserved Domains (2) summary
    pfam00300
    Location:252 → 435
    His_Phos_1; Histidine phosphatase superfamily (branch 1)
    pfam01591
    Location:26 → 249
    6PF2K; 6-phosphofructo-2-kinase

  4. XM_024447654.2 → XP_024303422.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 isoform X1

    UniProtKB/Swiss-Prot
    O60824, O60825, Q5VVQ3, Q5VVQ4, Q9H3P1
    Conserved Domains (2) summary
    pfam00300
    Location:252 → 435
    His_Phos_1; Histidine phosphatase superfamily (branch 1)
    pfam01591
    Location:26 → 249
    6PF2K; 6-phosphofructo-2-kinase

  5. XM_047422549.1 → XP_047278505.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 isoform X3

  6. XM_024447655.2 → XP_024303423.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 isoform X1

    UniProtKB/Swiss-Prot
    O60824, O60825, Q5VVQ3, Q5VVQ4, Q9H3P1
    Conserved Domains (2) summary
    pfam00300
    Location:252 → 435
    His_Phos_1; Histidine phosphatase superfamily (branch 1)
    pfam01591
    Location:26 → 249
    6PF2K; 6-phosphofructo-2-kinase

  7. XM_024447656.2 → XP_024303424.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 isoform X2

    UniProtKB/TrEMBL
    B0FLL2
    Conserved Domains (2) summary
    pfam01591
    Location:1 → 216
    6PF2K; 6-phosphofructo-2-kinase
    pfam00300
    Location:219 → 402
    His_Phos_1; Histidine phosphatase superfamily (branch 1)

  8. XM_005273162.4 → XP_005273219.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 isoform X4

    UniProtKB/TrEMBL
    Q68DE0
    Conserved Domains (1) summary
    pfam00300
    Location:10 → 193
    His_Phos_1; Histidine phosphatase superfamily (branch 1)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    206299607..206346250
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054337025.1 → XP_054193000.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 isoform X1

    UniProtKB/Swiss-Prot
    O60824, O60825, Q5VVQ3, Q5VVQ4, Q9H3P1

  2. XM_054337024.1 → XP_054192999.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 isoform X1

    UniProtKB/Swiss-Prot
    O60824, O60825, Q5VVQ3, Q5VVQ4, Q9H3P1

  3. XM_054337026.1 → XP_054193001.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 isoform X1

    UniProtKB/Swiss-Prot
    O60824, O60825, Q5VVQ3, Q5VVQ4, Q9H3P1

  4. XM_054337029.1 → XP_054193004.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 isoform X3

  5. XM_054337028.1 → XP_054193003.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 isoform X3

  6. XM_054337023.1 → XP_054192998.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 isoform X1

    UniProtKB/Swiss-Prot
    O60824, O60825, Q5VVQ3, Q5VVQ4, Q9H3P1

  7. XM_054337027.1 → XP_054193002.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 isoform X2

    UniProtKB/TrEMBL
    B0FLL2

  8. XM_054337030.1 → XP_054193005.1  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 isoform X4

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O60825.2 GenPept UniProtKB/Swiss-Prot:O60825

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