MGP Database

New search | Record Overview | Ontology/Pathway Information | Domain Information | UniProt Annotations | Related Proteins
MGP001101

UniProt Annotations

Entry Information
Gene Namefolylpolyglutamate synthase
Protein EntryFOLC_HUMAN
UniProt IDQ05932
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing, Alternative initiation; Named isoforms=4; Name=1; Synonyms=Mitochondrial; IsoId=Q05932-1; Sequence=Displayed; Name=2; Synonyms=Cytoplasmic; IsoId=Q05932-2; Sequence=VSP_018733; Note=Produced by alternative initiation at Met-43 of isoform 1.; Name=3; IsoId=Q05932-3; Sequence=VSP_018733, VSP_041959; Note=Produced by alternative splicing of isoform 1.; Name=4; IsoId=Q05932-4; Sequence=VSP_041960; Note=Produced by alternative splicing of isoform 1.;
Biophysicochemical PropertiesKinetic parameters: KM=201 uM for L-glutamate (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; KM=200 uM for MgATP (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; 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) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; KM=16 uM for PteGlu(2) (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; KM=20 uM for PteGlu(3) (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; KM=12 uM for PteGlu(4) (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; KM=64 uM for PteGlu(5) (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; 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) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; 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) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; 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) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; 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) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; 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) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; 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) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; 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) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; 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) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; 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) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; 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) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; 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) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; 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) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; 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) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; KM=4.4 uM for aminopterin (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; 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) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; 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) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; 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) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; 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) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; 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) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; 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) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; 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) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; 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) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; 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) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; 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) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; 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) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; 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) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; 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) {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720}; pH dependence: Optimum pH is 9.6 (isoform 2). {ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:8662720};
Catalytic ActivityATP + tetrahydropteroyl-(gamma-Glu)(n) + L- glutamate = ADP + phosphate + tetrahydropteroyl-(gamma-Glu)(n+1). {ECO:0000269|PubMed:1409616, ECO:0000269|PubMed:17875718, ECO:0000269|PubMed:18672898, ECO:0000269|PubMed:8408018, ECO:0000269|PubMed:8408020, ECO:0000269|PubMed:8662720}.
CofactorName=K(+); Xref=ChEBI:CHEBI:29103; Evidence={ECO:0000269|PubMed:8662720}; Name=NH4(+); Xref=ChEBI:CHEBI:28938; Evidence={ECO:0000269|PubMed:8662720}; Note=A monovalent cation. K(+) is most effective, followed by NH4(+) and Rb(+). Na(+), Li(+) and Cs(+) are ineffective. {ECO:0000269|PubMed:8662720};
Enzyme RegulationActivated by 10 mM sodium bicarbonate. {ECO:0000269|PubMed:8662720}.
FunctionCatalyzes 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. {ECO:0000269|PubMed:8408018, ECO:0000269|PubMed:8408019, ECO:0000269|PubMed:8408021, ECO:0000269|PubMed:8662720}.
PathwayCofactor biosynthesis; tetrahydrofolylpolyglutamate biosynthesis.
Sequence CautionSequence=AAA35852.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
SimilarityBelongs to the folylpolyglutamate synthase family. {ECO:0000305}.
Subcellular LocationIsoform 1: Mitochondrion inner membrane. Mitochondrion matrix.
Subcellular LocationIsoform 2: Cytoplasm.
SubunitMonomer.
  logo