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{{Infobox gene}}
{{PBB_Controls
'''6-phosphofructokinase, liver type''' (PFKL) is an [[enzyme]] that in humans is encoded by the ''PFKL'' [[gene]] on chromosome 21.<ref name="entrez">{{cite web | title = Entrez Gene: PFKL phosphofructokinase, liver| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5211| accessdate = }}</ref> This gene encodes the [[liver]] (L) [[protein subunit|subunit]] of an enzyme that [[catalyze]]s 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]<ref name="entrez" />
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| update_protein_box = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Structure ==
{{GNF_Protein_box
=== Gene ===
| image = 
| image_source = 
| PDB =
| Name = Phosphofructokinase, liver
| HGNCid = 8876
| Symbol = PFKL
| AltSymbols =; DKFZp686G1648; DKFZp686L2097; FLJ30173; FLJ40909; PFK-B
| OMIM = 171860
| ECnumber = 
| Homologene = 55668
| MGIid = 97547
| GeneAtlas_image1 = PBB_GE_PFKL_201102_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_PFKL_211065_x_at_tn.png
| GeneAtlas_image3 = PBB_GE_PFKL_214309_s_at_tn.png
| Function = {{GNF_GO|id=GO:0000166 |text = nucleotide binding}} {{GNF_GO|id=GO:0000287 |text = magnesium ion binding}} {{GNF_GO|id=GO:0003872 |text = 6-phosphofructokinase activity}} {{GNF_GO|id=GO:0005524 |text = ATP binding}} {{GNF_GO|id=GO:0016301 |text = kinase activity}} {{GNF_GO|id=GO:0016740 |text = transferase activity}}
| Component = {{GNF_GO|id=GO:0005737 |text = cytoplasm}} {{GNF_GO|id=GO:0005945 |text = 6-phosphofructokinase complex}}
| Process = {{GNF_GO|id=GO:0006002 |text = fructose 6-phosphate metabolic process}} {{GNF_GO|id=GO:0006096 |text = glycolysis}} {{GNF_GO|id=GO:0006110 |text = regulation of glycolysis}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 5211
    | Hs_Ensembl = ENSG00000141959
    | Hs_RefseqProtein = NP_001002021
    | Hs_RefseqmRNA = NM_001002021
    | Hs_GenLoc_db =
    | Hs_GenLoc_chr = 21
    | Hs_GenLoc_start = 44544358
    | Hs_GenLoc_end = 44571681
    | Hs_Uniprot = P17858
    | Mm_EntrezGene = 18641
    | Mm_Ensembl = ENSMUSG00000020277
    | Mm_RefseqmRNA = NM_008826
    | Mm_RefseqProtein = NP_032852
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 10
    | Mm_GenLoc_start = 77390400
    | Mm_GenLoc_end = 77412878
    | Mm_Uniprot = Q8CD98
  }}
}}
'''Phosphofructokinase, liver''', also known as '''PFKL''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: PFKL phosphofructokinase, liver| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5211| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
The PFKL mRNA sequence includes 55 [[nucleotide]]s at the [[5']] and 515 nucleotides at the [[3']] [[noncoding region]]s, as well as 2,337 nucleotides in the coding region, encoding 779 [[amino acid]]s. This coding region only shares a 68% similarity between PFKL and the muscle-type [[PFKM]].<ref name=pmid2533063>{{cite journal | vauthors = Levanon D, Danciger E, Dafni N, Bernstein Y, Elson A, Moens W, Brandeis M, Groner Y | title = The primary structure of human liver type phosphofructokinase and its comparison with other types of PFK | journal = Dna | volume = 8 | issue = 10 | pages = 733–43 | date = December 1989 | pmid = 2533063 | doi=10.1089/dna.1989.8.733}}</ref>
{{PBB_Summary
| section_title =
| summary_text = Phosphofructokinase (PFK) is a tetrameric enzyme that catalyzes a key step in glycolysis, namely the conversion of D-fructose 6-phosphate to D-fructose 1,6-bisphosphate. Separate genes encode a muscle subunit (M) and a liver subunit (L). PFK from muscle is a homotetramer of M subunits, PFK from liver is a homotetramer of L-subunits, while PFK from platelets can be composed of any tetrameric combination of M and L subunits. The protein encoded by this gene represents the L subunit. Two transcript variants encoding different isoforms have been found for this gene.<ref name="entrez">{{cite web | title = Entrez Gene: PFKL phosphofructokinase, liver| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5211| accessdate = }}</ref>
}}


==References==
=== Protein ===
{{reflist|2}}
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.<ref name=pmid6444721>{{cite journal | vauthors = Vora S, Seaman C, Durham S, Piomelli S | title = Isozymes of human phosphofructokinase: identification and subunit structural characterization of a new system | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 77 | issue = 1 | pages = 62–6 | date = Jan 1980 | pmid = 6444721 | doi=10.1073/pnas.77.1.62 | pmc=348208}}</ref><ref name=pmid6227635>{{cite journal | vauthors = Vora S, Davidson M, Seaman C, Miranda AF, Noble NA, Tanaka KR, Frenkel EP, Dimauro S | title = Heterogeneity of the molecular lesions in inherited phosphofructokinase deficiency | journal = The Journal of Clinical Investigation | volume = 72 | issue = 6 | pages = 1995–2006 | date = December 1983 | pmid = 6227635 | doi = 10.1172/JCI111164 | pmc=437040}}</ref> The muscle isozyme ([[PFK-1]]) is composed solely of PFKM.<ref name=pmid6444721/><ref name=pmid6445244>{{cite journal | vauthors = Koster JF, Slee RG, Van Berkel TJ | title = Isoenzymes of human phosphofructokinase | journal = Clinica Chimica Acta; International Journal of Clinical Chemistry | volume = 103 | issue = 2 | pages = 169–73 | date = April 1980 | pmid = 6445244 | doi=10.1016/0009-8981(80)90210-7}}</ref><ref name=pmid22133655>{{cite journal | vauthors = Musumeci O, Bruno C, Mongini T, Rodolico C, Aguennouz M, Barca E, Amati A, Cassandrini D, Serlenga L, Vita G, Toscano A | title = Clinical features and new molecular findings in muscle phosphofructokinase deficiency (GSD type VII) | journal = Neuromuscular Disorders | volume = 22 | issue = 4 | pages = 325–30 | date = April 2012 | pmid = 22133655 | doi = 10.1016/j.nmd.2011.10.022 }}</ref> 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<ref name=pmid22474333>{{cite journal | vauthors = Brüser A, Kirchberger J, Kloos M, Sträter N, Schöneberg T | title = Functional linkage of adenine nucleotide binding sites in mammalian muscle 6-phosphofructokinase | journal = The Journal of Biological Chemistry | volume = 287 | issue = 21 | pages = 17546–53 | date = May 2012 | pmid = 22474333 | doi = 10.1074/jbc.M112.347153 | pmc=3366854}}</ref>
==Further reading==
 
{{refbegin | 2}}
== Function ==
{{PBB_Further_reading
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.<ref name=pmid6444721/><ref name=pmid22133655/><ref name=pmid22474333/><ref name=pmid26194095>{{cite journal | vauthors = Graham DB, Becker CE, Doan A, Goel G, Villablanca EJ, Knights D, Mok A, Ng AC, Doench JG, Root DE, Clish CB, Xavier RJ | title = Functional genomics identifies negative regulatory nodes controlling phagocyte oxidative burst | journal = Nature Communications | volume = 6 | pages = 7838 | date = 21 July 2015 | pmid = 26194095 | doi = 10.1038/ncomms8838 | pmc=4518307}}</ref> Notably, [[Gene knockdown|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.<ref name=pmid26194095/>
| citations =  
 
*{{cite journal  | author=Kahn A, Meienhofer MC, Cottreau D, ''et al.'' |title=Phosphofructokinase (PFK) isozymes in man. I. Studies of adult human tissues. |journal=Hum. Genet. |volume=48 |issue= 1 |pages= 93-108 |year= 1979 |pmid= 156693 |doi= }}
PFKL has also been detected in [[leukocyte]]s, [[kidney]], and [[brain]].<ref name=pmid6445244/>
*{{cite journal | author=Kristensen T, Lopez R, Prydz H |title=An estimate of the sequencing error frequency in the DNA sequence databases. |journal=DNA Seq. |volume=2 |issue= 6 |pages= 343-6 |year= 1992 |pmid= 1446073 |doi= }}
 
*{{cite journal | author=Wang D, Fang H, Cantor CR, Smith CL |title=A contiguous Not I restriction map of band q22.3 of human chromosome 21. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=89 |issue= 8 |pages= 3222-6 |year= 1992 |pmid= 1565613 |doi= }}
== Clinical significance ==
*{{cite journal | author=Elson A, Levanon D, Brandeis M, ''et al.'' |title=The structure of the human liver-type phosphofructokinase gene. |journal=Genomics |volume=7 |issue= 1 |pages= 47-56 |year= 1990 |pmid= 2139864 |doi= }}
As the erythrocyte PFK is composed of both PFKL and PFKM, this [[Homogeneity and heterogeneity#Heterogeneity|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).<ref name=pmid6444721/><ref name=pmid6227635/>
*{{cite journal | author=Levanon D, Danciger E, Dafni N, ''et al.'' |title=The primary structure of human liver type phosphofructokinase and its comparison with other types of PFK. |journal=DNA |volume=8 |issue= 10 |pages= 733-43 |year= 1990 |pmid= 2533063 |doi= }}
 
*{{cite journal  | author=Van Keuren M, Drabkin H, Hart I, ''et al.'' |title=Regional assignment of human liver-type 6-phosphofructokinase to chromosome 21q22.3 by using somatic cell hybrids and a monoclonal anti-L antibody. |journal=Hum. Genet. |volume=74 |issue= 1 |pages= 34-40 |year= 1986 |pmid= 2944814 |doi= }}
Overexpression of PFKL has been associated with [[Down's syndrome]] (DS) erythrocytes and [[fibroblast]]s 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.<ref name=pmid1533471>{{cite journal | vauthors = Elson A, Bernstein Y, Degani H, Levanon D, Ben-Hur H, Groner Y | title = Gene dosage and Down's syndrome: metabolic and enzymatic changes in PC12 cells overexpressing transfected human liver-type phosphofructokinase | journal = Somatic Cell and Molecular Genetics | volume = 18 | issue = 2 | pages = 143–61 | date = March 1992 | pmid = 1533471 | doi=10.1007/bf01233161}}</ref>
*{{cite journal  | author=Levanon D, Danciger E, Dafni N, Groner Y |title=Genomic clones of the human liver-type phosphofructokinase. |journal=Biochem. Biophys. Res. Commun. |volume=141 |issue= 1 |pages= 374-80 |year= 1987 |pmid= 2948503 |doi=  }}
 
*{{cite journal  | author=Vora S, Davidson M, Seaman C, ''et al.'' |title=Heterogeneity of the molecular lesions in inherited phosphofructokinase deficiency. |journal=J. Clin. Invest. |volume=72 |issue= 6 |pages= 1995-2006 |year= 1984 |pmid= 6227635 |doi= }}
== Interactive pathway map ==
*{{cite journal  | author=Vora S, Seaman C, Durham S, Piomelli S |title=Isozymes of human phosphofructokinase: identification and subunit structural characterization of a new system. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=77 |issue= 1 |pages= 62-6 |year= 1980 |pmid= 6444721 |doi=  }}
{{GlycolysisGluconeogenesis_WP534|highlight=PFKL}}
*{{cite journal  | author=Koster JF, Slee RG, Van Berkel TJ |title=Isoenzymes of human phosphofructokinase. |journal=Clin. Chim. Acta |volume=103 |issue= 2 |pages= 169-73 |year= 1980 |pmid= 6445244 |doi=  }}
 
*{{cite journal  | author=Vora S, Francke U |title=Assignment of the human gene for liver-type 6-phosphofructokinase isozyme (PFKL) to chromosome 21 by using somatic cell hybrids and monoclonal anti-L antibody. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=78 |issue= 6 |pages= 3738-42 |year= 1981 |pmid= 6455664 |doi=  }}
== Model organisms ==
*{{cite journal  | author=Zeitschel U, Bigl M, Eschrich K, Bigl V |title=Cellular distribution of 6-phosphofructo-1-kinase isoenzymes in rat brain. |journal=J. Neurochem. |volume=67 |issue= 6 |pages= 2573-80 |year= 1996 |pmid= 8931492 |doi=  }}
{| class="wikitable sortable collapsible collapsed" border="1" cellpadding="2" style="float: right;" |
*{{cite journal  | author=Hattori M, Fujiyama A, Taylor TD, ''et al.'' |title=The DNA sequence of human chromosome 21. |journal=Nature |volume=405 |issue= 6784 |pages= 311-9 |year= 2000 |pmid= 10830953 |doi= 10.1038/35012518 }}
|+ ''Pfkl'' knockout mouse phenotype
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
|-
*{{cite journal  | author=Gevaert K, Goethals M, Martens L, ''et al.'' |title=Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. |journal=Nat. Biotechnol. |volume=21 |issue= 5 |pages= 566-9 |year= 2004 |pmid= 12665801 |doi= 10.1038/nbt810 }}
! Characteristic!! Phenotype
*{{cite journal  | author=Zhang C, Dowd DR, Staal A, ''et al.'' |title=Nuclear coactivator-62 kDa/Ski-interacting protein is a nuclear matrix-associated coactivator that may couple vitamin D receptor-mediated transcription and RNA splicing. |journal=J. Biol. Chem. |volume=278 |issue= 37 |pages= 35325-36 |year= 2003 |pmid= 12840015 |doi= 10.1074/jbc.M305191200 }}
 
*{{cite journal  | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
|-
*{{cite journal  | author=Colland F, Jacq X, Trouplin V, ''et al.'' |title=Functional proteomics mapping of a human signaling pathway. |journal=Genome Res. |volume=14 |issue= 7 |pages= 1324-32 |year= 2004 |pmid= 15231748 |doi= 10.1101/gr.2334104 }}
| [[Homozygote]] viability || bgcolor="#C40000"|Abnormal
*{{cite journal | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
|-
*{{cite journal | author=Rush J, Moritz A, Lee KA, ''et al.'' |title=Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. |journal=Nat. Biotechnol. |volume=23 |issue= 1 |pages= 94-101 |year= 2005 |pmid= 15592455 |doi= 10.1038/nbt1046 }}
| [[Recessive]] lethal study || bgcolor="#C40000"|Abnormal
}}
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| Fertility || bgcolor="#488ED3"|Normal
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| Body weight || bgcolor="#488ED3"|Normal
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| [[Open Field (animal test)|Anxiety]] || bgcolor="#488ED3"|Normal
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| Neurological assessment || bgcolor="#488ED3"|Normal
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| Grip strength || bgcolor="#488ED3"|Normal
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| [[Hot plate test|Hot plate]] || bgcolor="#488ED3"|Normal
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| [[Dysmorphology]] || bgcolor="#488ED3"|Normal
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| [[Indirect calorimetry]] || bgcolor="#488ED3"|Normal
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| [[Glucose tolerance test]] || bgcolor="#488ED3"|Normal
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| [[Auditory brainstem response]] || bgcolor="#488ED3"|Normal
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| [[Dual-energy X-ray absorptiometry|DEXA]] || bgcolor="#488ED3"|Normal
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| [[Radiography]] || bgcolor="#488ED3"|Normal
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| Body temperature || bgcolor="#488ED3"|Normal
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| Eye morphology || bgcolor="#488ED3"|Normal
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| [[Clinical chemistry]] || bgcolor="#488ED3"|Normal
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| [[Haematology]] || bgcolor="#488ED3"|Normal
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| [[Peripheral blood lymphocyte]]s || bgcolor="#488ED3"|Normal
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| [[Micronucleus test]] || bgcolor="#488ED3"|Normal
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| Heart weight || bgcolor="#488ED3"|Normal
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| Tail epidermis wholemount || bgcolor="#488ED3"|Normal
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| Skin Histopathology || bgcolor="#C40000"|Abnormal
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| Brain histopathology || bgcolor="#488ED3"|Normal
|-
| ''[[Salmonella]]'' infection || bgcolor="#488ED3"|Normal<ref name="''Salmonella'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBCL/salmonella-challenge/ |title=''Salmonella'' infection data for Pfkl |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| ''[[Citrobacter]]'' infection || bgcolor="#488ED3"|Normal<ref name="''Citrobacter'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBCL/citrobacter-challenge/ |title=''Citrobacter'' infection data for Pfkl |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| colspan=2; style="text-align: center;" | All tests and analysis from<ref name="mgp_reference">{{cite journal | doi = 10.1111/j.1755-3768.2010.4142.x | title = The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice | year = 2010 | author = Gerdin AK | journal = Acta Ophthalmologica | volume = 88 | pages = 925–7 }}</ref><ref>[http://www.sanger.ac.uk/mouseportal/ Mouse Resources Portal], Wellcome Trust Sanger Institute.</ref>
|}
[[Model organism]]s have been used in the study of PFKL function. A conditional [[knockout mouse]] line, called ''Pfkl<sup>tm1a(EUCOMM)Wtsi</sup>''<ref name="allele_ref">{{cite web |url=http://www.knockoutmouse.org/martsearch/search?query=Pfkl |title=International Knockout Mouse Consortium}}</ref><ref name="mgi_allele_ref">{{cite web |url=http://www.informatics.jax.org/searchtool/Search.do?query=MGI:4432814 |title=Mouse Genome Informatics}}</ref> was generated as part of the [[International Knockout Mouse Consortium]] program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.<ref name="pmid21677750">{{cite journal | vauthors = Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A | title = A conditional knockout resource for the genome-wide study of mouse gene function | journal = Nature | volume = 474 | issue = 7351 | pages = 337–42 | date = June 2011 | pmid = 21677750 | pmc = 3572410 | doi = 10.1038/nature10163 }}</ref><ref name="mouse_library">{{cite journal | vauthors = Dolgin E | title = Mouse library set to be knockout | journal = Nature | volume = 474 | issue = 7351 | pages = 262–3 | date = June 2011 | pmid = 21677718 | doi = 10.1038/474262a }}</ref><ref name="mouse_for_all_reasons">{{cite journal | vauthors = Collins FS, Rossant J, Wurst W | title = A mouse for all reasons | journal = Cell | volume = 128 | issue = 1 | pages = 9–13 | date = Jan 2007 | pmid = 17218247 | doi = 10.1016/j.cell.2006.12.018 }}</ref>
 
Male and female animals underwent a standardized [[phenotypic screen]] to determine the effects of deletion.<ref name="mgp_reference" /><ref name="pmid21722353">{{cite journal | vauthors = van der Weyden L, White JK, Adams DJ, Logan DW | title = The mouse genetics toolkit: revealing function and mechanism | journal = Genome Biology | volume = 12 | issue = 6 | pages = 224 | year = 2011 | pmid = 21722353 | pmc = 3218837 | doi = 10.1186/gb-2011-12-6-224 }}</ref> Twenty six tests were carried out on [[mutant]] mice and three significant abnormalities were observed.<ref name="mgp_reference" />  Few [[homozygous]] [[mutant]] embryos were identified during gestation, and none survived until [[weaning]]. The remaining tests were carried out on [[heterozygous]] mutant adult mice and a [[hair follicle]] degeneration phenotype was observed.<ref name="mgp_reference" />
 
== See also ==
*[[PFK]]
*[[PFKM]]
*[[PFKP]]
 
== References ==
{{reflist|33em}}
 
== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = Kahn A, Meienhofer MC, Cottreau D, Lagrange JL, Dreyfus JC | title = Phosphofructokinase (PFK) isozymes in man. I. Studies of adult human tissues | journal = Human Genetics | volume = 48 | issue = 1 | pages = 93–108 | date = April 1979 | pmid = 156693 | doi = 10.1007/bf00273280 }}
* {{cite journal | vauthors = Kristensen T, Lopez R, Prydz H | title = An estimate of the sequencing error frequency in the DNA sequence databases | journal = DNA Sequence | volume = 2 | issue = 6 | pages = 343–6 | year = 1992 | pmid = 1446073 | doi = 10.3109/10425179209020815 }}
* {{cite journal | vauthors = Wang D, Fang H, Cantor CR, Smith CL | title = A contiguous Not I restriction map of band q22.3 of human chromosome 21 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 8 | pages = 3222–6 | date = April 1992 | pmid = 1565613 | pmc = 48838 | doi = 10.1073/pnas.89.8.3222 }}
* {{cite journal | vauthors = Elson A, Levanon D, Brandeis M, Dafni N, Bernstein Y, Danciger E, Groner Y | title = The structure of the human liver-type phosphofructokinase gene | journal = Genomics | volume = 7 | issue = 1 | pages = 47–56 | date = May 1990 | pmid = 2139864 | doi = 10.1016/0888-7543(90)90517-X }}
* {{cite journal | vauthors = Levanon D, Danciger E, Dafni N, Bernstein Y, Elson A, Moens W, Brandeis M, Groner Y | title = The primary structure of human liver type phosphofructokinase and its comparison with other types of PFK | journal = Dna | volume = 8 | issue = 10 | pages = 733–43 | date = December 1989 | pmid = 2533063 | doi = 10.1089/dna.1989.8.733 }}
* {{cite journal | vauthors = Van Keuren M, Drabkin H, Hart I, Harker D, Patterson D, Vora S | title = Regional assignment of human liver-type 6-phosphofructokinase to chromosome 21q22.3 by using somatic cell hybrids and a monoclonal anti-L antibody | journal = Human Genetics | volume = 74 | issue = 1 | pages = 34–40 | date = September 1986 | pmid = 2944814 | doi = 10.1007/bf00278782 }}
* {{cite journal | vauthors = Levanon D, Danciger E, Dafni N, Groner Y | title = Genomic clones of the human liver-type phosphofructokinase | journal = Biochemical and Biophysical Research Communications | volume = 141 | issue = 1 | pages = 374–80 | date = November 1986 | pmid = 2948503 | doi = 10.1016/S0006-291X(86)80379-5 }}
* {{cite journal | vauthors = Vora S, Davidson M, Seaman C, Miranda AF, Noble NA, Tanaka KR, Frenkel EP, Dimauro S | title = Heterogeneity of the molecular lesions in inherited phosphofructokinase deficiency | journal = The Journal of Clinical Investigation | volume = 72 | issue = 6 | pages = 1995–2006 | date = December 1983 | pmid = 6227635 | pmc = 437040 | doi = 10.1172/JCI111164 }}
* {{cite journal | vauthors = Vora S, Seaman C, Durham S, Piomelli S | title = Isozymes of human phosphofructokinase: identification and subunit structural characterization of a new system | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 77 | issue = 1 | pages = 62–6 | date = Jan 1980 | pmid = 6444721 | pmc = 348208 | doi = 10.1073/pnas.77.1.62 }}
* {{cite journal | vauthors = Koster JF, Slee RG, Van Berkel TJ | title = Isoenzymes of human phosphofructokinase | journal = Clinica Chimica Acta; International Journal of Clinical Chemistry | volume = 103 | issue = 2 | pages = 169–73 | date = April 1980 | pmid = 6445244 | doi = 10.1016/0009-8981(80)90210-7 }}
* {{cite journal | vauthors = Vora S, Francke U | title = Assignment of the human gene for liver-type 6-phosphofructokinase isozyme (PFKL) to chromosome 21 by using somatic cell hybrids and monoclonal anti-L antibody | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 78 | issue = 6 | pages = 3738–42 | date = June 1981 | pmid = 6455664 | pmc = 319647 | doi = 10.1073/pnas.78.6.3738 }}
* {{cite journal | vauthors = Zeitschel U, Bigl M, Eschrich K, Bigl V | title = Cellular distribution of 6-phosphofructo-1-kinase isoenzymes in rat brain | journal = Journal of Neurochemistry | volume = 67 | issue = 6 | pages = 2573–80 | date = December 1996 | pmid = 8931492 | doi = 10.1046/j.1471-4159.1996.67062573.x }}
* {{cite journal | vauthors = Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J | title = Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides | journal = Nature Biotechnology | volume = 21 | issue = 5 | pages = 566–9 | date = May 2003 | pmid = 12665801 | doi = 10.1038/nbt810 }}
* {{cite journal | vauthors = Zhang C, Dowd DR, Staal A, Gu C, Lian JB, van Wijnen AJ, Stein GS, MacDonald PN | title = Nuclear coactivator-62 kDa/Ski-interacting protein is a nuclear matrix-associated coactivator that may couple vitamin D receptor-mediated transcription and RNA splicing | journal = The Journal of Biological Chemistry | volume = 278 | issue = 37 | pages = 35325–36 | date = September 2003 | pmid = 12840015 | doi = 10.1074/jbc.M305191200 }}
* {{cite journal | vauthors = Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM | title = Functional proteomics mapping of a human signaling pathway | journal = Genome Research | volume = 14 | issue = 7 | pages = 1324–32 | date = July 2004 | pmid = 15231748 | pmc = 442148 | doi = 10.1101/gr.2334104 }}
* {{cite journal | vauthors = Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ | title = Immunoaffinity profiling of tyrosine phosphorylation in cancer cells | journal = Nature Biotechnology | volume = 23 | issue = 1 | pages = 94–101 | date = Jan 2005 | pmid = 15592455 | doi = 10.1038/nbt1046 }}
{{refend}}
{{refend}}


{{Kinases}}
{{Glycolysis enzymes}}
{{Use dmy dates|date=April 2017}}


{{gene-21-stub}}
[[Category:Genes mutated in mice]]
{{WikiDoc Sources}}

Latest revision as of 17:59, 7 September 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

6-phosphofructokinase, liver type (PFKL) is an enzyme that in humans is encoded by the PFKL gene on chromosome 21.[1] This gene encodes the liver (L) subunit of 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][1]

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.[2]

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.[3][4] The muscle isozyme (PFK-1) is composed solely of PFKM.[3][5][6] 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[7]

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.[3][6][7][8] 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.[8]

PFKL has also been detected in leukocytes, kidney, and brain.[5]

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).[3][4]

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.[9]

Interactive pathway map

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

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Glycolysis and Gluconeogenesis edit
  1. ↑ The interactive pathway map can be edited at WikiPathways: "GlycolysisGluconeogenesis_WP534".

Model organisms

Model organisms have been used in the study of PFKL function. A conditional knockout mouse line, called Pfkltm1a(EUCOMM)Wtsi[14][15] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[16][17][18]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[12][19] Twenty six tests were carried out on mutant mice and three significant abnormalities were observed.[12] Few homozygous mutant embryos were identified during gestation, and none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and a hair follicle degeneration phenotype was observed.[12]

See also

References

  1. ↑ 1.0 1.1 "Entrez Gene: PFKL phosphofructokinase, liver".
  2. ↑ Levanon D, Danciger E, Dafni N, Bernstein Y, Elson A, Moens W, Brandeis M, Groner Y (December 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.
  3. ↑ 3.0 3.1 3.2 3.3 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. doi:10.1073/pnas.77.1.62. PMC 348208. PMID 6444721.
  4. ↑ 4.0 4.1 Vora S, Davidson M, Seaman C, Miranda AF, Noble NA, Tanaka KR, Frenkel EP, Dimauro S (December 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.
  5. ↑ 5.0 5.1 Koster JF, Slee RG, Van Berkel TJ (April 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.
  6. ↑ 6.0 6.1 Musumeci O, Bruno C, Mongini T, Rodolico C, Aguennouz M, Barca E, Amati A, Cassandrini D, Serlenga L, Vita G, Toscano A (April 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.
  7. ↑ 7.0 7.1 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.
  8. ↑ 8.0 8.1 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. doi:10.1038/ncomms8838. PMC 4518307. PMID 26194095.
  9. ↑ Elson A, Bernstein Y, Degani H, Levanon D, Ben-Hur H, Groner Y (March 1992). "Gene dosage and Down's syndrome: metabolic and enzymatic changes in PC12 cells overexpressing transfected human liver-type phosphofructokinase". Somatic Cell and Molecular Genetics. 18 (2): 143–61. doi:10.1007/bf01233161. PMID 1533471.
  10. ↑ "Salmonella infection data for Pfkl". Wellcome Trust Sanger Institute.
  11. ↑ "Citrobacter infection data for Pfkl". Wellcome Trust Sanger Institute.
  12. ↑ 12.0 12.1 12.2 12.3 Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  13. ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  14. ↑ "International Knockout Mouse Consortium".
  15. ↑ "Mouse Genome Informatics".
  16. ↑ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (June 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  17. ↑ Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  18. ↑ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  19. ↑ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading

Retrieved from "https://www.wikidoc.org/index.php?title=PFKL&oldid=1419823"