PFKM
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4OMT
Identifiers
Aliases	PFKM, ATP-PFK, GSD7, PFK-1, PFK1, PFKA, PFKX, PPP1R122, phosphofructokinase, muscle
External IDs	OMIM: 610681; MGI: 97548; HomoloGene: 20101; GeneCards: PFKM; OMA: PFKM - orthologs
Gene location ( Mouse) Chr. Chromosome 15 (mouse) [1] Band 15|15 F1 Start 97,990,470 bp [1] End 98,030,332 bp [1]
RNA expression pattern Bgee Human Mouse (ortholog) n/a Top expressed in triceps brachii muscle temporal muscle extensor digitorum longus muscle ankle sternocleidomastoid muscle medial head of gastrocnemius muscle tibialis anterior muscle digastric muscle vastus lateralis muscle muscle of thigh BioGPS More reference expression data
Gene ontology Molecular function transferase activity nucleotide binding protein homodimerization activity metal ion binding kinase activity fructose binding kinase binding protein C-terminus binding catalytic activity protein binding identical protein binding phosphofructokinase activity ATP binding 6-phosphofructokinase activity AMP binding monosaccharide binding fructose-6-phosphate binding Cellular component cytoplasm cytosol 6-phosphofructokinase complex sperm principal piece apical plasma membrane nucleus membrane Biological process fructose 6-phosphate metabolic process glycolysis from storage polysaccharide through glucose-1-phosphate glycolytic process muscle cell cellular homeostasis glucose homeostasis phosphorylation canonical glycolysis carbohydrate phosphorylation glycogen catabolic process protein complex oligomerization metabolism positive regulation of insulin secretion positive regulation of transcription by RNA polymerase II glycolytic process through fructose-6-phosphate glucose catabolic process fructose 1,6-bisphosphate metabolic process protein homotetramerization Sources: Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5213 18642 Ensembl ENSG00000152556 ENSMUSG00000033065 UniProt P08237 P47857 RefSeq (mRNA) NM_000289 NM_001166686 NM_001166687 NM_001166688 NM_001163487 NM_001163488 NM_021514 NM_001357688 RefSeq (protein) NP_000280 NP_001160158 NP_001160159 NP_001160160 NP_001341664 NP_001341666 NP_001341667 NP_001341668 NP_001341669 NP_001341670 NP_001341671 NP_001341672 NP_001341673 NP_001341674 NP_001341675 NP_001341676 NP_001341677 NP_001341665 NP_001350548 NP_001156959 NP_001156960 NP_067489 NP_001344617 Location (UCSC) n/a Chr 15: 97.99 – 98.03 Mb PubMed search [2] [3]
Wikidata
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6-phosphofructokinase, muscle type is an enzyme that in humans is encoded by the PFKM gene on chromosome 12. Three phosphofructokinase isozymes exist in humans: muscle, liver and platelet. These isozymes function as subunits of the mammalian tetramer phosphofructokinase, which catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate. Tetramer composition varies depending on tissue type. This gene encodes the muscle-type isozyme. Mutations in this gene have been associated with glycogen storage disease type VII, also known as Tarui disease. Alternatively spliced transcript variants have been described.[provided by RefSeq, Nov 2009] ^[4]

Structure

Gene

This gene is found on chromosome 12. ^[4] The coding region in PFKM only shares a 68% similarity with that of the liver-type PFKL. ^[5]

Protein

This 85-kDa protein is one of two subunit types that comprise the seven tetrameric PFK isozymes. ^{[6] [7]} The muscle isozyme ( PFK-1) is composed solely of PFKM. ^{[6] [8] [9]} The liver PFK (PFK-5) contains solely the second subunit type, PFKL, while the erythrocyte PFK includes five isozymes composed of different combinations of PFKM and PFKL. ^{[6] [7] [9]} 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. ^[10] In particular, the binding site for the PFK inhibitor citrate is found in the PFKL C-terminal region. ^[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. ^{[6] [9] [10] [12]}

Though the PFKM subunit majorly incorporates into muscle and erythrocyte PFKs, PFKM also is expressed in the heart, brain, and testis. ^[13]

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, also known as Tarui disease. ^{[6] [9] [14]} Notably, mutations in PFKM have been shown to cause Tarui disease due to homozygosity for catalytically inactive M subunits. ^{[7] [14]} PFKM is confirmed to be involved in muscle PFK deficiency with early-onset hyperuricemia. ^[7]

Even though PFKM functions to drive glycolysis, its overexpression has been associated with type 2 diabetes and insulin resistance in skeletal muscle. One possible explanation suggests that the overexpression is meant to compensate for the allosteric inhibition of PFK1 as a result of excess oxidation of free fatty acids and accumulation of citrate and acetyl-CoA. ^[14]

Interactions

PFKM has been shown to interact with ATP6V0A4. ^[15]

Interactive pathway map

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

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|alt=Glycolysis and Gluconeogenesis ]]

Glycolysis and Gluconeogenesis

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

See also

• PFK
• PFK-1
• PFKL
• PFKP

References

Further reading