Names & Taxonomy

Uniprot ID:
Q05932
Entry Name:
FOLC_HUMAN
Status:
reviewed
Protein Names:
Folylpolyglutamate synthase, mitochondrial (EC 6.3.2.17) (Folylpoly-gamma-glutamate synthetase) (FPGS) (Tetrahydrofolylpolyglutamate synthase) (Tetrahydrofolate synthase)
Gene Names:
FPGS
Gene Names Primary:
FPGS
Organism:
Homo sapiens (Human)

Structure

Length:
587
Sequence:
MSRARSHLRAALFLAAASARGITTQVAARRGLSAWPVPQEPSMEYQDAVRMLNTLQTNAGYLEQVKRQRGDPQTQLEAMELYLARSGLQVEDLDRLNIIHVTGTKGKGSTCAFTECILRSYGLKTGFFSSPHLVQVRERIRINGQPISPELFTKYFWRLYHRLEETKDGSCVSMPPYFRFLTLMAFHVFLQEKVDLAVVEVGIGGAYDCTNIIRKPVVCGVSSLGIDHTSLLGDTVEKIAWQKGGIFKQGVPAFTVLQPEGPLAVLRDRAQQISCPLYLCPMLEALEEGGPPLTLGLEGEHQRSNAALALQLAHCWLQRQDRHGAGEPKASRPGLLWQLPLAPVFQPTSHMRLGLRNTEWPGRTQVLRRGPLTWYLDGAHTASSAQACVRWFRQALQGRERPSGGPEVRVLLFNATGDRDPAALLKLLQPCQFDYAVFCPNLTEVSSTGNADQQNFTVTLDQVLLRCLEHQQHWNHLDEEQASPDLWSAPSPEPGGSASLLLAPHPPHTCSASSLVFSCISHALQWISQGRDPIFQPPSPPKGLLTHPVAHSGASILREAAAIHVLVTGSLHLVGGVLKLLEPALSQ
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Isoform 1: Mitochondrion inner membrane

Function

Function:
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. Unsubstituted reduced folates are the preferred substrates. Metabolizes methotrexate (MTX) to polyglutamates.
Pathway:
Cofactor biosynthesis; tetrahydrofolylpolyglutamate biosynthesis.
Catalytic Activity:
ATP + tetrahydropteroyl-(gamma-Glu)(n) + L-glutamate = ADP + phosphate + tetrahydropteroyl-(gamma-Glu)(n+1).
Cofactor:
COFACTOR: Name=K(+); Xref=ChEBI:CHEBI:29103;
Kinetics:
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic 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)
Enzyme Regulation:
ENZYME REGULATION: Activated by 10 mM sodium bicarbonate.
Cross Reference Drug Bank:
DB00563 DB06813 DB00293
Gene Ontology Go:
cytoplasm
cytosol
mitochondrial inner membrane
mitochondrial matrix
mitochondrion
ATP binding
tetrahydrofolylpolyglutamate synthase activity
brain development
cell proliferation
folic acid metabolic process
folic acid-containing compound metabolic process
glutamate metabolic process
liver development
nucleobase-containing compound metabolic process
one-carbon metabolic process
organ regeneration
small molecule metabolic process
tetrahydrofolylpolyglutamate biosynthetic process
vitamin metabolic process
water-soluble vitamin metabolic process
Gene Ontology Biological Process:
brain development
cell proliferation
folic acid-containing compound metabolic process
folic acid metabolic process
glutamate metabolic process
liver development
nucleobase-containing compound metabolic process
one-carbon metabolic process
organ regeneration
small molecule metabolic process
tetrahydrofolylpolyglutamate biosynthetic process
vitamin metabolic process
water-soluble vitamin metabolic process
Gene Ontology Molecular Function:
ATP binding
tetrahydrofolylpolyglutamate synthase activity
Gene Ontology Cellular Component:
cytoplasm
cytosol
mitochondrial inner membrane
mitochondrial matrix
mitochondrion
Keywords:
ATP-binding
Acetylation
Alternative initiation
Alternative splicing
Complete proteome
Cytoplasm
Ligase
Membrane
Mitochondrion
Mitochondrion inner membrane
Nucleotide-binding
One-carbon metabolism
Polymorphism
Reference proteome
Transit peptide

Publication

PubMed ID:
14702039 15164053 15489334 8662720 7721888 1409616 8521387 8408018 8408019 8408020 8408021 16169100 17875718 18672898 22814378