Phosphatase Subfamily PFKFB - Revision history

Gerard at 21:50, 25 October 2016

2016-10-25T21:50:28Z

Gerard at 16:51, 15 May 2016

2016-05-15T16:51:48Z

Gerard at 16:45, 15 May 2016

2016-05-15T16:45:58Z

Mark: /* Evolution */

2015-06-02T18:50:28Z

‎Evolution

Mark at 18:50, 2 June 2015

2015-06-02T18:50:14Z

Mark: /* Functions */

2015-06-02T18:49:51Z

‎Functions

Mark: /* Catalytic activity */

2015-06-02T18:44:27Z

‎Catalytic activity

Mark: /* Catalytic activity */

2015-06-02T18:24:46Z

‎Catalytic activity

Mark: /* Evolution */

2015-06-02T18:24:14Z

‎Evolution

Mark at 18:21, 2 June 2015

2015-06-02T18:21:22Z

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 __NOTOC__
-[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_HP|Fold HP]]: [[Phosphatase_Superfamily_HP|Superfamily HP]] (histidine phosphatase):  [[Phosphatase_Family_HP1|HP, branch1 family]]: [[Phosphatase_Subfamily_PFKFB|Subfamily PFKFB]]
+[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_HP|Fold HP]]: [[Phosphatase_Superfamily_HP|Superfamily HP]]:  [[Phosphatase_Family_HP1|HP, branch1 family]]: [[Phosphatase_Subfamily_PFKFB|Subfamily PFKFB]]
 PFKFB is a dual kinase and phosphatase that both phosphorylates and dephosphorylates fructose to fructose 2,6-bisphosphate (Fru-2,6-P2). Fru-2,6-P2 is an allosteric activator of the key glycolysis enzyme phosphofructokinase 1 (Pfk1), so PKFKB activities both activate and deactivate glycolysis.

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 [[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_HP|Fold HP]]: [[Phosphatase_Superfamily_HP|Superfamily HP]] (histidine phosphatase):  [[Phosphatase_Family_HP1|HP, branch1 family]]: [[Phosphatase_Subfamily_PFKFB|Subfamily PFKFB]]
-PFKFB stands for PFK-2 (6-phosphofructo-2-kinase)/ FBPase-2 (fructose-2,6-bisphosphatase), which catalyses both the synthesis and degradation of fructose 2,6-bisphosphate (Fru-2,6-P2). Fru-2,6-P2 is a signal molecule that controls glycolysis.
+PFKFB is a dual kinase and phosphatase that both phosphorylates and dephosphorylates fructose to fructose 2,6-bisphosphate (Fru-2,6-P2). Fru-2,6-P2 is an allosteric activator of the key glycolysis enzyme phosphofructokinase 1 (Pfk1), so PKFKB activities both activate and deactivate glycolysis.
 === Evolution ===
-PFKFB has two enzymatic domains responsible for the synthesis and hydrolysis, 6-phosphofructo-2-kinase (PFK-2) and fructose-2,6-bisphosphatase (FBPase-2). Both domains are present in all major eukaryotic groups. Phylogenetic analysis suggests that PFKFB emerged through gene fusion event that happened in a common ancestor of all extant eukaryotes. Two distinct genes encoding PFK-2 and FBPase-2, or related enzymes with broader substrate specificity, fused resulting in a bifunctional enzyme both domains of which had, or later acquired, specificity for fructose 2,6-bisphosphate <cite>rider04, michel06</cite>.
+PFKFB is found in most eukaryotic groups, and is thought to result from an early fusion of it's two enzymatic domains (6-phosphofructo-2-kinase (PFK-2) and fructose-2,6-bisphosphatase (FBPase-2). Two distinct genes encoding PFK-2 and FBPase-2, or related enzymes with broader substrate specificity, fused resulting in a bifunctional enzyme both domains of which had, or later acquired, specificity for fructose 2,6-bisphosphate <cite>rider04, michel06</cite>.
 This enzyme is duplicated in many lineages, sometimes losing either kinase or phosphatase activity in the duplicates, and in some parasitic lineages, the gene is lost entirely <cite>michel06</cite>
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 === Functions ===
-PFKFB is a homodimeric bifunctional enzyme that catalyses both the synthesis and degradation of Fru-2,6-P2 (fructose 2,6-bisphosphate) during glycolysis  <cite>rider04, michel06</cite>. Fru-2,6,-P2 is also the substrate of [[Phosphatase_Subfamily_TIGAR|Subfamily TIGAR]], another subfamily of HP1 phosphatases.
+PFKFB is a homodimeric bifunctional enzyme that catalyses both the synthesis and degradation of Fru-2,6-P2 (fructose 2,6-bisphosphate) during glycolysis  <cite>rider04, michel06</cite>. Fru-2,6-P2 is also the substrate of [[Phosphatase_Subfamily_TIGAR|Subfamily TIGAR]], another subfamily of HP1 phosphatases.
 The four human PFKFBs have slightly different gene expression across different tissues. PFKFB3 has an isoform-specific S-glutathionylation, which mediates its functions in regulating oxidative stress homeostasis <cite>Seo14</cite>.

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 === Evolution ===
-PFKFB has two enzymatic domains responsible for the synthesis and hydrolysis, 6-phosphofructo-2-kinase (PFK-2) and fructose-2,6-bisphosphatase (FBPase-2). Both domains are present in all major eukaryotic groups. Previous bioinformatics analysis suggested that PFKFB emerged through gene fusion event that happened in a common ancestor of all extant eukaryotes. Two distinct genes encoding PFK-2 and FBPase-2, or related enzymes with broader substrate specificity, fused resulting in a bifunctional enzyme both domains of which had, or later acquired, specificity for fructose 2,6-bisphosphate <cite>rider04, michel06</cite>.
+PFKFB has two enzymatic domains responsible for the synthesis and hydrolysis, 6-phosphofructo-2-kinase (PFK-2) and fructose-2,6-bisphosphatase (FBPase-2). Both domains are present in all major eukaryotic groups. Phylogenetic analysis suggests that PFKFB emerged through gene fusion event that happened in a common ancestor of all extant eukaryotes. Two distinct genes encoding PFK-2 and FBPase-2, or related enzymes with broader substrate specificity, fused resulting in a bifunctional enzyme both domains of which had, or later acquired, specificity for fructose 2,6-bisphosphate <cite>rider04, michel06</cite>.
-Multiple copies are found in the genomes of different phylogenetic lineages, which emerged through gene duplications, independently in different lineages of many unicellular eukaryotes. In some lineages, one of the domains of the different PFK-2/FBPase-2 isoforms has undergone substitutions of critical catalytic residues or deletions of the whole domain, which rendered some enzymes monofunctional. In a considerable number of other unicellular eukaryotes, mainly parasitic organisms, the enzyme seems to have been lost altogether.
+This enzyme is duplicated in many lineages, sometimes losing either kinase or phosphatase activity in the duplicates, and in some parasitic lineages, the gene is lost entirely <cite>michel06</cite>
 === Domain ===
 PFKFB has two domains for its two functions  <cite>rider04, michel06</cite>:
-* The kinase PFK-2 domain for synthesis of Fru-2,6-P2, has the same fold with adenylate kinase, confirmed by crystal structure.
+* The kinase PFK-2 domain for synthesis of Fru-2,6-P2, has an adenylate kinase fold, confirmed by crystal structure.
-* The phosphatase FBPase-2 domain for degradation of Fru-2,6,-P2 is a HP2 domain, evidenced by sequence, mechanistic and structural similarity with histidine phosphatases.
+* The phosphatase FBPase-2 domain for degradation of Fru-2,6-P2 is a HP1 domain.
 === Functions ===
-PFKFB is a homodimeric bifunctional enzyme that catalyses both the synthesis and degradation of Fru-2,6-P2 (fructose 2,6-bisphosphate) that is a signal molecule that controls glycolysis  <cite>rider04, michel06</cite>. Fru-2,6,-P2 is also the substrate of TIGAR, another subfamily in HP1 family.
+PFKFB is a homodimeric bifunctional enzyme that catalyses both the synthesis and degradation of Fru-2,6-P2 (fructose 2,6-bisphosphate) during glycolysis  <cite>rider04, michel06</cite>. Fru-2,6,-P2 is also the substrate of [[Phosphatase_Subfamily_TIGAR|Subfamily TIGAR]], another subfamily of HP1 phosphatases.
 The four human PFKFBs have slightly different gene expression across different tissues. PFKFB3 has an isoform-specific S-glutathionylation, which mediates its functions in regulating oxidative stress homeostasis <cite>Seo14</cite>.

@@ Line 5: / Line 5: @@
 === Evolution ===
-PFKFB has two enzymatic domains responsible for the synthesis and hydrolysis, 6-phosphofructo-2-kinase (PFK-2) and fructose-2,6-bisphosphatase (FBPase-2). Both domains are present in all major eukaryotic groups. Previous bioinformatics analysis suggested that PFKFB emerged through gene fusion event that happened in a common ancestor of all extant eukaryotes. Two distinct genes encoding PFK-2 and FBPase-2, or related enzymes with broader substrate specificity, fused resulting in a bifunctional enzyme both domains of which had, or later acquired, specificity for fructose 2,6-bisphosphate <cite>rider04, michels06</cite>.
+PFKFB has two enzymatic domains responsible for the synthesis and hydrolysis, 6-phosphofructo-2-kinase (PFK-2) and fructose-2,6-bisphosphatase (FBPase-2). Both domains are present in all major eukaryotic groups. Previous bioinformatics analysis suggested that PFKFB emerged through gene fusion event that happened in a common ancestor of all extant eukaryotes. Two distinct genes encoding PFK-2 and FBPase-2, or related enzymes with broader substrate specificity, fused resulting in a bifunctional enzyme both domains of which had, or later acquired, specificity for fructose 2,6-bisphosphate <cite>rider04, michel06</cite>.
 Multiple copies are found in the genomes of different phylogenetic lineages, which emerged through gene duplications, independently in different lineages of many unicellular eukaryotes. In some lineages, one of the domains of the different PFK-2/FBPase-2 isoforms has undergone substitutions of critical catalytic residues or deletions of the whole domain, which rendered some enzymes monofunctional. In a considerable number of other unicellular eukaryotes, mainly parasitic organisms, the enzyme seems to have been lost altogether.

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 <biblio>
 #rider04 pmid=15170386
 #michel06 pmid=16766380
 </biblio>

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 PFKFB is a homodimeric bifunctional enzyme that catalyses both the synthesis and degradation of Fru-2,6-P2 (fructose 2,6-bisphosphate) that is a signal molecule that controls glycolysis  <cite>rider04, michel06</cite>.
-(PS: functional redundancy within PFKFBs and between PFKFB and TIGAR? They have different tissue expression pattern according to GTEx and in literature.)
+PS: functional redundancy within PFKFBs and between PFKFB and TIGAR? They have different tissue expression pattern according to GTEx and in literature.
 === References ===