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MGP002255

UniProt Annotations

Entry Information
Gene Namephosphofructokinase, liver
Protein EntryPFKAL_HUMAN
UniProt IDP17858
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=P17858-1; Sequence=Displayed; Name=2; Synonyms=a; IsoId=P17858-2; Sequence=VSP_011854; Note=No experimental confirmation available.;
Catalytic ActivityATP + D-fructose 6-phosphate = ADP + D- fructose 1,6-bisphosphate. {ECO:0000255|HAMAP-Rule:MF_03184, ECO:0000269|PubMed:22923583}.
CofactorName=Mg(2+); Xref=ChEBI:CHEBI:18420;
Enzyme RegulationAllosterically activated by ADP, AMP, or fructose 2,6-bisphosphate, and allosterically inhibited by ATP or citrate. GlcNAcylation by OGT overcomes allosteric regulation. {ECO:0000255|HAMAP-Rule:MF_03184, ECO:0000269|PubMed:22923583}.
FunctionCatalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis. {ECO:0000255|HAMAP-Rule:MF_03184, ECO:0000269|PubMed:22923583}.
InteractionSelf; NbExp=2; IntAct=EBI-487243, EBI-487243; P08237:PFKM; NbExp=6; IntAct=EBI-487243, EBI-514788;
MiscellaneousGlycosylation may play a role in cancer cell proliferation: inhibition of 6-phosphofructokinase activity and subsequent redirection of the glucose flux through the oxidative pentose phosphate pathway confers a selective growth advantage on cancer cells. Moreover GlcNAcylation is observed in multiple cancer cell lines and tissue samples and GlcNAcylation leads to larger xenografts tunors in mice (PubMed:22923583). {ECO:0000305|PubMed:22923583}.
MiscellaneousIn human PFK exists as a system of 3 types of subunits, PFKM (muscle), PFKL (liver) and PFKP (platelet) isoenzymes.
PathwayCarbohydrate degradation; glycolysis; D-glyceraldehyde 3- phosphate and glycerone phosphate from D-glucose: step 3/4. {ECO:0000255|HAMAP-Rule:MF_03184}.
PtmGlcNAcylation at Ser-529 by OGT decreases enzyme activity, leading to redirect glucose flux through the oxidative pentose phosphate pathway. Glycosylation is stimulated by both hypoxia and glucose deprivation. {ECO:0000269|PubMed:22923583}.
SimilarityBelongs to the phosphofructokinase type A (PFKA) family. ATP-dependent PFK group I subfamily. Eukaryotic two domain clade "E" sub-subfamily. {ECO:0000255|HAMAP-Rule:MF_03184}.
Subcellular LocationCytoplasm {ECO:0000255|HAMAP-Rule:MF_03184}.
SubunitHomo- and heterotetramers. Muscle is M4, liver is L4, and red cell is M3L, M2L2, or ML3.
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