PFKL
Identifiers
Aliases	PFKL, ATP-PFK, PFK-B, PFK-L, phosphofructokinase, liver type
External IDs	OMIM: 171860 MGI: 97547 HomoloGene: 55668 GeneCards: PFKL
Gene location (Human) Chr. Chromosome 21 (human)[1] Band 21q22.3 Start 44,300,051 bp[1] End 44,327,376 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10 C1|10 39.72 cM Start 77,822,781 bp[2] End 77,845,917 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in tibial nerve skin of abdomen body of stomach canal of the cervix right uterine tube amygdala right lobe of liver nucleus accumbens minor salivary glands gastric mucosa Top expressed in brown adipose tissue primitive streak entorhinal cortex somite retinal pigment epithelium pyloric antrum superior frontal gyrus otic placode epithelium of stomach atrium More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity nucleotide binding monosaccharide binding metal ion binding kinase activity fructose binding kinase binding protein binding catalytic activity identical protein binding ATP binding 6-phosphofructokinase activity fructose-6-phosphate binding AMP binding Cellular component cytoplasm membrane 6-phosphofructokinase complex extracellular exosome cytosol extracellular region secretory granule lumen ficolin-1-rich granule lumen Biological process negative regulation of insulin secretion phosphorylation canonical glycolysis protein complex oligomerization metabolism glycolytic process through fructose-6-phosphate protein homotetramerization glycolytic process fructose 6-phosphate metabolic process fructose 1,6-bisphosphate metabolic process response to glucose neutrophil degranulation carbohydrate metabolic process glucose catabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5211 18641 Ensembl ENSG00000141959 ENSMUSG00000020277 UniProt P17858 Q7L2M7 P12382 RefSeq (mRNA) NM_001002021 NM_002626 NM_008826 NM_001358793 RefSeq (protein) NP_001002021 NP_002617 NP_001002021.2 NP_002617.3 NP_032852 NP_001345722 Location (UCSC) Chr 21: 44.3 – 44.33 Mb Chr 10: 77.82 – 77.85 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

6-phosphofructokinase, liver type (PFKL) is an enzyme that in humans is encoded by the PFKL gene on chromosome 21.^[5] This gene encodes the liver (L) isoform of phosphofructokinase-1, an enzyme that catalyzes the conversion of D-fructose 6-phosphate to D-fructose 1,6-bisphosphate, which is a key step in glucose metabolism (glycolysis). This enzyme is a tetramer that may be composed of different subunits encoded by distinct genes in different tissues. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]^[5]

Structure

Gene

The PFKL mRNA sequence includes 55 nucleotides at the 5' and 515 nucleotides at the 3' noncoding regions, as well as 2,337 nucleotides in the coding region, encoding 779 amino acids. This coding region only shares a 68% similarity between PFKL and the muscle-type PFKM.^[6]

Protein

This 80-kDa protein is one of three subunit types that comprise the five tetrameric PFK isozymes. The liver PFK (PFK-5) contains solely PFKL, while the erythrocyte PFK includes five isozymes composed of different combinations of PFKL and the second subunit type, PFKM.^[7][8] The muscle isozyme (PFK-1) is composed solely of PFKM.^[7][9][10] These subunits evolved from a common prokaryotic ancestor via gene duplication and mutation events. Generally, the N-terminal of the subunits carries out their catalytic activity while the C-terminal contains allosteric ligand binding sites^[11]

Function

This gene encodes one of three protein subunits of PFK, which are expressed and combined to form the tetrameric PFK in a tissue-specific manner. As a PFK subunit, PFKL is involved in catalyzing the phosphorylation of fructose 6-phosphate to fructose 1,6-bisphosphate. This irreversible reaction serves as the major rate-limiting step of glycolysis.^{[7][10][11][12]} Notably, knockdown of PFKL has been shown to impair glycolysis and promote metabolism via the pentose phosphate pathway. Moreover, PFKL regulates NADPH oxidase activity through the pentose phosphate pathway and according to NADPH levels.^[12]

PFKL has also been detected in leukocytes, kidney, and brain.^[9]

Clinical significance

As the erythrocyte PFK is composed of both PFKL and PFKM, this heterogeneic composition is attributed with the differential PFK activity and organ involvement observed in some inherited PFK deficiency states in which myopathy or hemolysis or both can occur, such as glycogenosis type VII (Tarui disease).^[7][8]

Overexpression of PFKL has been associated with Down's syndrome (DS) erythrocytes and fibroblasts and attributed with biochemical changes in PFK that enhance its glycolytic function. Moreover, the PFKL gene maps to the triplicated region of chromosome 21 responsible for DS, indicating that this gene, too, has been triplicated.^[13]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles.^{[§ 1]}

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|alt=Glycolysis and Gluconeogenesis edit]]

Glycolysis and Gluconeogenesis edit

1. ^ The interactive pathway map can be edited at WikiPathways: "GlycolysisGluconeogenesis_WP534".