FPGS - Folylpolyglutamate synthase, mitochondrial - human protein (Function)
 
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Protein
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References

 
FPGS »  Folylpolyglutamate synthase, mitochondrial   [ EC 6.3.2.17 ]
 
Protein also known as:  Tetrahydrofolylpolyglutamate synthase (Tetrahydrofolate synthase).
Gene name:  FPGS
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
Catalyzes conversion of folates to polyglutamate derivatives allowing concentration of folate compounds in the cell and the intracellular retention of these cofactors, which are important substrates for most of the folate-dependent enzymes that are involved in one-carbon transfer reactions involved in purine, pyrimidine and amino acid synthesis. Unsubstitued reduced folates are the preferred substrates. Metabolizes methotrexate (MTX) to polyglutamates.  
4
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Tetrahydrofolylpolyglutamate synthase activitydefinition[GO:0004326]  
  • IEAEC 2 GO
GO biological process 
Brain developmentdefinition[GO:0007420] silver  
  • IEAOrtholog Compara
Liver developmentdefinition[GO:0001889] silver  
  • IEAOrtholog Compara
Nucleobase-containing compound metabolic processdefinition[GO:0006139]  
1
  • TASPINC
One-carbon metabolic processdefinition[GO:0006730]  
  • IEAUniProtKB KW
Organ regenerationdefinition[GO:0031100] silver  
  • IEAOrtholog Compara
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 6.3.2.17: ATP + tetrahydropteroyl-(gamma-Glu)(n) + L-glutamate ADP + phosphate + tetrahydropteroyl-(gamma-Glu)(n+1).  
6
  • CuratedUniProtKB
It requires the following cofactor
A monovalent cation. K(+) is most effective, followed by NH4(+) and Rb(+). Na(+), Li(+) and Cs(+) are ineffective.  
1
  • CuratedUniProtKB
It is regulated in the following manner
Activated by 10 mM sodium bicarbonate.  
1
  • CuratedUniProtKB
Pathways 
This protein is involved in the following pathway
According to KEGG, this protein belongs to the following pathways:
Folate biosynthesis  hsa00790+2356  
Metabolic pathways  hsa01100+2356  
According to Reactome, this protein belongs to the following pathways:
Disease  REACT_116125  
Metabolism  REACT_111217  
 
More information is available from:
 

Biophysicochemical properties

Kinetic parameters
KM 1.6 uM for (6ambo)-tetrahydropteroylpoly-gamma-glutamate (H(4)PteGlu) (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)
KM 50 uM for methotrexate (Glu-2) (isoform 2, PubMed:8662720, at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)
KM 4.4 uM for (6S)-H(4)PteGlu (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)
KM 16 uM for PteGlu(2) (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)
KM 59 uM for pteroylglutamic acid (PteGlu) (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)
KM 3.3 uM for (6S)-H(4)PteGlu(2) (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)
KM 1702 uM for glutamic acid (isoform 2, PubMed:17875718, at 37 degrees Celsius in the presence of 10 mM ATP and pH 8.5)
KM 55.5 uM for methotrexate (isoform 2, PubMed:17875718, at 37 degrees Celsius in the presence of 10 mM ATP and pH 8.5)
KM 2.7 uM for (6R)-10-formyl-H(4)PteGlu(2) (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)
KM 5.3 uM for 5-deazaacyclotetrahydrofolate (isoform 2, at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)
KM 64 uM for PteGlu(5) (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)
KM 148 uM for methotrexate (Glu-3) (isoform 2, PubMed:8662720, at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)
KM 71 uM for methotrexate (Glu-1) (isoform 2, PubMed:8662720, at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)
KM 12 uM for PteGlu(4) (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)
KM 200 uM for MgATP (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)
KM 2.8 uM for 2-methyl-5,8-dideazaisofolate (isoform 2, at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)
KM 1.4 uM for (6S)-H(4)PteGlu(3) (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)
KM 105 uM for (6S)-5-formyl-H(4)PteGlu (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)
KM 47 uM for H(2)PteGlu(2) (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)
KM 4.4 uM for aminopterin (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)
KM 1.4 uM for (6S)-H(4)PteGlu(5) (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)
KM 3.7 uM for (6R)-10-formyl-H(4)PteGlu (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)
KM 2068 uM for glutamic acid (isoform 1, PubMed:17875718, at 37 degrees Celsius in the presence of 10 mM ATP and pH 8.5)
KM 13 uM for (6S)-5-formyl-H(4)PteGlu(2) (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)
KM 20 uM for PteGlu(3) (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)
KM 0.81 uM for H(2)PteGlu (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)
KM 1.6 uM for (6S)-H(4)PteGlu(4) (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)
KM 201 uM for L-glutamate (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)
KM 48 uM for (6S)-5-methyl-H(4)PteGlu (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)
KM 52.6 uM for methotrexate (isoform 1, PubMed:17875718, at 37 degrees Celsius in the presence of 10 mM ATP and pH 8.5)
Vmax 0.05 umol/h/mg enzyme with methotrexate as substrate (isoform 1, PubMed:17875718, at 37 degrees Celsius in the presence of 10 mM ATP and pH 8.5)
Vmax 1.26 umol/h/mg enzyme with glutamic acid as substrate (isoform 2, PubMed:17875718, at 37 degrees Celsius in the presence of 10 mM ATP and pH 8.5)
Vmax 0.25 umol/h/mg enzyme with glutamic acid as substrate (isoform 1, PubMed:17875718, at 37 degrees Celsius in the presence of 10 mM ATP and pH 8.5)
Vmax 0.34 umol/h/mg enzyme with methotrexate as substrate (isoform 2, PubMed:17875718, at 37 degrees Celsius in the presence of 10 mM ATP and pH 8.5)
Dependence
pH Optimum pH is 9.6 (isoform 2).

Keywords

Biological process 
One-carbon metabolism  definition   [KW-0554]
Molecular function 
Ligase  definition   [KW-0436]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: FPGS
GenomeRNAi: 2356
PRO: PR:Q05932