Hmdb loader
Identification
HMDB Protein ID HMDBP00849
Secondary Accession Numbers
  • 6130
  • HMDBP03851
  • HMDBP07374
Name Folylpolyglutamate synthase, mitochondrial
Synonyms
  1. FPGS
  2. Folylpoly-gamma-glutamate synthetase
  3. Tetrahydrofolate synthase
  4. Tetrahydrofolylpolyglutamate synthase
Gene Name FPGS
Protein Type Enzyme
Biological Properties
General Function Involved in tetrahydrofolylpolyglutamate synthase activity
Specific 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. Unsubstitued reduced folates are the preferred substrates. Metabolizes methotrexate (MTX) to polyglutamates.
Pathways
  • Folate biosynthesis
  • Folate malabsorption, hereditary
  • Methotrexate Action Pathway
  • Methylenetetrahydrofolate Reductase Deficiency (MTHFRD)
  • One carbon pool by folate
  • Pterine Biosynthesis
  • tetrahydrofolylpolyglutamate biosynthesis
Reactions
Adenosine triphosphate + tetrahydropteroyl-(gamma-Glu)(n) + L-Glutamic acid → ADP + Phosphate + tetrahydropteroyl-(gamma-Glu)(n+1) details
Adenosine triphosphate + Tetrahydrofolic acid + L-Glutamic acid → ADP + Phosphate + Tetrahydrofolyl-[Glu](2) details
Adenosine triphosphate + 7,8-Dihydropteroic acid + L-Glutamic acid → ADP + Phosphate + Dihydrofolic acid details
Adenosine triphosphate + + L-Glutamic acid → ADP + Phosphate + details
GO Classification
Biological Process
folic acid metabolic process
nucleobase-containing compound metabolic process
one-carbon metabolic process
Cellular Component
cytosol
mitochondrial matrix
mitochondrial inner membrane
Function
binding
catalytic activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
ligase activity
ligase activity, forming carbon-nitrogen bonds
acid-amino acid ligase activity
tetrahydrofolylpolyglutamate synthase activity
Molecular Function
tetrahydrofolylpolyglutamate synthase activity
ATP binding
Process
metabolic process
cellular aromatic compound metabolic process
folic acid and derivative metabolic process
cellular metabolic process
biosynthetic process
folic acid and derivative biosynthetic process
Cellular Location
  1. Cytoplasm
  2. Mitochondrion
Gene Properties
Chromosome Location 9
Locus 9q34.1
SNPs FPGS
Gene Sequence
>1764 bp
ATGTCGCGGGCGCGGAGCCACCTGCGCGCCGCTCTATTCCTGGCAGCGGCGTCTGCGCGC
GGCGTAACGACCCAGGTCGCGGCGCGGCGGGGCTTGAGCGCGTGGCCGGTGCCGCAGGAG
CCGAGCATGGAGTACCAGGATGCCGTGCGCATGCTCAATACCCTGCAGACCAATGCCGGC
TACCTGGAGCAGGTGAAGCGCCAGCGGGGTGACCCTCAGACACAGTTGGAAGCCATGGAA
CTGTACCTGGCACGGAGTGGGCTGCAGGTGGAGGACTTGGACCGGCTGAACATCATCCAC
GTCACTGGGACGAAGGGGAAGGGCTCCACCTGTGCCTTCACGGAATGTATCCTCCGAAGC
TATGGCCTGAAGACGGGATTCTTTAGCTCTCCCCACCTGGTGCAGGTTCGGGAGCGGATC
CGCATCAATGGGCAGCCCATCAGTCCTGAGCTCTTCACCAAGTACTTCTGGCGCCTCTAC
CACCGGCTGGAGGAGACCAAGGATGGCAGCTGTGTCTCCATGCCCCCCTACTTCCGCTTC
CTGACACTCATGGCCTTCCACGTCTTCCTCCAAGAGAAGGTGGACCTGGCAGTGGTGGAG
GTGGGCATTGGCGGGGCTTATGACTGCACCAACATCATCAGGAAGCCTGTGGTGTGCGGA
GTCTCCTCTCTTGGCATCGACCACACCAGCCTCCTGGGGGATACGGTGGAGAAGATCGCA
TGGCAGAAAGGGGGCATCTTTAAGCAAGGTGTCCCTGCCTTCACTGTGCTCCAACCTGAA
GGTCCCCTGGCAGTGCTGAGGGACCGAGCCCAGCAGATCTCATGTCCTCTATACCTGTGT
CCGATGCTGGAGGCCCTCGAGGAAGGGGGGCCGCCGCTGACCCTGGGCCTGGAGGGGGAG
CACCAGCGGTCCAACGCCGCCTTGGCCTTGCAGCTGGCCCACTGCTGGCTGCAGCGGCAG
GACCGCCATGGTGCTGGGGAGCCAAAGGCATCCAGGCCAGGGCTCCTGTGGCAGCTGCCC
CTGGCACCTGTGTTCCAGCCCACATCCCACATGCGGCTCGGGCTTCGGAACACGGAGTGG
CCGGGCCGGACGCAGGTGCTGCGGCGCGGGCCCCTCACCTGGTACCTGGACGGTGCGCAC
ACCGCCAGCAGCGCGCAGGCCTGCGTGCGCTGGTTCCGCCAGGCGCTGCAGGGCCGCGAG
AGGCCGAGCGGTGGCCCCGAGGTTCGAGTCTTGCTCTTCAATGCTACCGGGGACCGGGAC
CCGGCGGCCCTGCTGAAGCTGCTGCAGCCCTGCCAGTTTGACTATGCCGTCTTCTGCCCT
AACCTGACAGAGGTGTCATCCACAGGCAACGCAGACCAACAGAACTTCACAGTGACACTG
GACCAGGTCCTGCTCCGCTGCCTGGAACACCAGCAGCACTGGAACCACCTGGACGAAGAG
CAGGCCAGCCCGGACCTCTGGAGTGTCCCCAGCCCAGAGCCCGGTGGGTCCGCATCCCTG
CTTCTGGCGCCCCACCCACCCCACACCTGCAGTGCCAGCTCCCTCGTCTTCAGCTGCATT
TCACATGCCTTGCAATGGATCAGCCAAGGCCGAGACCCCATCTTCCAGCCACCTAGTCCC
CCAAAGGGCCTCCTCACCCACCCTGTGGCTCACAGTGGGGCCAGCATACTCCGTGAGGCT
GCTGCCATCCATGTGCTAGTCACTGGCAGCCTGCACCTGGTGGGTGGTGTCCTGAAGCTG
CTGGAGCCCGCACTGTCCCAGTAG
Protein Properties
Number of Residues 587
Molecular Weight 59173.37
Theoretical pI 7.399
Pfam Domain Function Not Available
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Folylpolyglutamate synthase, mitochondrial
MSRARSHLRAALFLAAASARGITTQVAARRGLSAWPVPQEPSMEYQDAVRMLNTLQTNAG
YLEQVKRQRGDPQTQLEAMELYLARSGLQVEDLDRLNIIHVTGTKGKGSTCAFTECILRS
YGLKTGFFSSPHLVQVRERIRINGQPISPELFTKYFWRLYHRLEETKDGSCVSMPPYFRF
LTLMAFHVFLQEKVDLAVVEVGIGGAYDCTNIIRKPVVCGVSSLGIDHTSLLGDTVEKIA
WQKGGIFKQGVPAFTVLQPEGPLAVLRDRAQQISCPLYLCPMLEALEEGGPPLTLGLEGE
HQRSNAALALQLAHCWLQRQDRHGAGEPKASRPGLLWQLPLAPVFQPTSHMRLGLRNTEW
PGRTQVLRRGPLTWYLDGAHTASSAQACVRWFRQALQGRERPSGGPEVRVLLFNATGDRD
PAALLKLLQPCQFDYAVFCPNLTEVSSTGNADQQNFTVTLDQVLLRCLEHQQHWNHLDEE
QASPDLWSAPSPEPGGSASLLLAPHPPHTCSASSLVFSCISHALQWISQGRDPIFQPPSP
PKGLLTHPVAHSGASILREAAAIHVLVTGSLHLVGGVLKLLEPALSQ
GenBank ID Protein 39992602
UniProtKB/Swiss-Prot ID Q05932
UniProtKB/Swiss-Prot Entry Name FOLC_HUMAN
PDB IDs Not Available
GenBank Gene ID BC064393
GeneCard ID FPGS
GenAtlas ID FPGS
HGNC ID HGNC:3824
References
General References
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  2. Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blocker H, Durbin R, Sulston JE, Hubbard T, Jackson MJ, Bentley DR, Beck S, Rogers J, Dunham I: DNA sequence and analysis of human chromosome 9. Nature. 2004 May 27;429(6990):369-74. [PubMed:15164053 ]
  3. Garrow TA, Admon A, Shane B: Expression cloning of a human cDNA encoding folylpoly(gamma-glutamate) synthetase and determination of its primary structure. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9151-5. [PubMed:1409616 ]
  4. Freemantle SJ, Taylor SM, Krystal G, Moran RG: Upstream organization of and multiple transcripts from the human folylpoly-gamma-glutamate synthetase gene. J Biol Chem. 1995 Apr 21;270(16):9579-84. [PubMed:7721888 ]
  5. Taylor SM, Freemantle SJ, Moran RG: Structural organization of the human folypoly-gamma-glutamate synthetase gene: evidence for a single genomic locus. Cancer Res. 1995 Dec 15;55(24):6030-4. [PubMed:8521387 ]
  6. Cichowicz DJ, Shane B: Mammalian folylpoly-gamma-glutamate synthetase. 1. Purification and general properties of the hog liver enzyme. Biochemistry. 1987 Jan 27;26(2):504-12. [PubMed:3828320 ]