PFKM

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PFKM
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPFKM, ATP-PFK, GSD7, PFK-1, PFK1, PFKA, PFKX, PPP1R122, phosphofructokinase, muscle
External IDsOMIM: 610681 MGI: 97548 HomoloGene: 20101 GeneCards: PFKM
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000289
NM_001166686
NM_001166687
NM_001166688

NM_001163487
NM_001163488
NM_021514
NM_001357688

RefSeq (protein)

NP_001156959
NP_001156960
NP_067489
NP_001344617

Location (UCSC)n/aChr 15: 97.99 – 98.03 Mb
PubMed search[2][3]
Wikidata
View/Edit HumanView/Edit Mouse

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]

[[File:
GlycolysisGluconeogenesis_WP534go to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to WikiPathwaysgo to articlego to Entrezgo to article
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GlycolysisGluconeogenesis_WP534go to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to WikiPathwaysgo to articlego to Entrezgo to article
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Glycolysis and Gluconeogenesis edit
  1. ^ The interactive pathway map can be edited at WikiPathways: "GlycolysisGluconeogenesis_WP534".

See also

References

  1. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000033065 - Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ a b "Entrez Gene: PFKM phosphofructokinase, muscle".
  5. ^ Levanon D, Danciger E, Dafni N, Bernstein Y, Elson A, Moens W, Brandeis M, Groner Y (Dec 1989). "The primary structure of human liver type phosphofructokinase and its comparison with other types of PFK". DNA. 8 (10): 733–43. doi:10.1089/dna.1989.8.733. PMID 2533063.
  6. ^ a b c d e Vora S, Seaman C, Durham S, Piomelli S (Jan 1980). "Isozymes of human phosphofructokinase: identification and subunit structural characterization of a new system". Proceedings of the National Academy of Sciences of the United States of America. 77 (1): 62–6. Bibcode:1980PNAS...77...62V. doi:10.1073/pnas.77.1.62. PMC 348208. PMID 6444721.
  7. ^ a b c d Vora S, Davidson M, Seaman C, Miranda AF, Noble NA, Tanaka KR, Frenkel EP, Dimauro S (Dec 1983). "Heterogeneity of the molecular lesions in inherited phosphofructokinase deficiency". The Journal of Clinical Investigation. 72 (6): 1995–2006. doi:10.1172/JCI111164. PMC 437040. PMID 6227635.
  8. ^ Koster JF, Slee RG, Van Berkel TJ (Apr 1980). "Isoenzymes of human phosphofructokinase". Clinica Chimica Acta; International Journal of Clinical Chemistry. 103 (2): 169–73. doi:10.1016/0009-8981(80)90210-7. PMID 6445244.
  9. ^ a b c d Musumeci O, Bruno C, Mongini T, Rodolico C, Aguennouz M, Barca E, Amati A, Cassandrini D, Serlenga L, Vita G, Toscano A (Apr 2012). "Clinical features and new molecular findings in muscle phosphofructokinase deficiency (GSD type VII)". Neuromuscular Disorders. 22 (4): 325–30. doi:10.1016/j.nmd.2011.10.022. PMID 22133655. S2CID 20133199.
  10. ^ a b Brüser A, Kirchberger J, Kloos M, Sträter N, Schöneberg T (May 2012). "Functional linkage of adenine nucleotide binding sites in mammalian muscle 6-phosphofructokinase". The Journal of Biological Chemistry. 287 (21): 17546–53. doi:10.1074/jbc.M112.347153. PMC 3366854. PMID 22474333.
  11. ^ Usenik A, Legiša M (23 November 2010). "Evolution of allosteric citrate binding sites on 6-phosphofructo-1-kinase". PLOS ONE. 5 (11): e15447. Bibcode:2010PLoSO...515447U. doi:10.1371/journal.pone.0015447. PMC 2990764. PMID 21124851.
  12. ^ Graham DB, Becker CE, Doan A, Goel G, Villablanca EJ, Knights D, Mok A, Ng AC, Doench JG, Root DE, Clish CB, Xavier RJ (21 July 2015). "Functional genomics identifies negative regulatory nodes controlling phagocyte oxidative burst". Nature Communications. 6: 7838. Bibcode:2015NatCo...6.7838G. doi:10.1038/ncomms8838. PMC 4518307. PMID 26194095.
  13. ^ Kahn A, Meienhofer MC, Cottreau D, Lagrange JL, Dreyfus JC (Apr 1979). "Phosphofructokinase (PFK) isozymes in man. I. Studies of adult human tissues". Human Genetics. 48 (1): 93–108. doi:10.1007/bf00273280. PMID 156693. S2CID 23300861.
  14. ^ a b c Keildson S, Fadista J, Ladenvall C, Hedman ÅK, Elgzyri T, Small KS, Grundberg E, Nica AC, Glass D, Richards JB, Barrett A, Nisbet J, Zheng HF, Rönn T, Ström K, Eriksson KF, Prokopenko I, Spector TD, Dermitzakis ET, Deloukas P, McCarthy MI, Rung J, Groop L, Franks PW, Lindgren CM, Hansson O (Mar 2014). "Expression of phosphofructokinase in skeletal muscle is influenced by genetic variation and associated with insulin sensitivity". Diabetes. 63 (3): 1154–65. doi:10.2337/db13-1301. PMC 3931395. PMID 24306210.
  15. ^ Su Y, Zhou A, Al-Lamki RS, Karet FE (May 2003). "The a-subunit of the V-type H+-ATPase interacts with phosphofructokinase-1 in humans". The Journal of Biological Chemistry. 278 (22): 20013–8. doi:10.1074/jbc.M210077200. PMID 12649290.

Further reading