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FPGS Gene

protein-coding   GIFtS: 65
GCID: GC09P130556

Folylpolyglutamate Synthase

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(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Folylpolyglutamate Synthase1 2
Folylpoly-Gamma-Glutamate Synthetase2 3
Tetrahydrofolate Synthase2 3
Tetrahydrofolylpolyglutamate Synthase2 3
EC 6.3.2.173 8
Folylpolyglutamate Synthase, Mitochondrial2

External Ids:    HGNC: 38241   Entrez Gene: 23562   Ensembl: ENSG000001368777   OMIM: 1365105   UniProtKB: Q059323   

Export aliases for FPGS gene to outside databases

Previous GC identifers: GC09P121679 GC09P122211 GC09P124018 GC09P125941 GC09P127644 GC09P129604 GC09P100181


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for FPGS Gene:
This gene encodes the folylpolyglutamate synthetase enzyme. This enzyme has a central role in establishing and
maintaining both cytosolic and mitochondrial folylpolyglutamate concentrations and, therefore, is essential for
folate homeostasis and the survival of proliferating cells. This enzyme catalyzes the ATP-dependent addition of
glutamate moieties to folate and folate derivatives. Alternative splicing results in transcript variants encoding
different isoforms. (provided by RefSeq, Jan 2014)

GeneCards Summary for FPGS Gene:
FPGS (folylpolyglutamate synthase) is a protein-coding gene. Diseases associated with FPGS include childhood leukemia, and malignant pleural mesothelioma. GO annotations related to this gene include tetrahydrofolylpolyglutamate synthase activity.

UniProtKB/Swiss-Prot: FOLC_HUMAN, Q05932
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

Gene Wiki entry for FPGS Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000009.12  NT_008470.20  NC_018920.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the FPGS gene promoter:
         p53   p300   ATF   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidFPGS promoter sequence
   Search Chromatin IP Primers for FPGS

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat FPGS


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 9q34.1   Ensembl cytogenetic band:  9q34.11   HGNC cytogenetic band: 9q34.11

FPGS Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
FPGS gene location

GeneLoc information about chromosome 9         GeneLoc Exon Structure

GeneLoc location for GC09P130556:  view genomic region     (about GC identifiers)

Start:
130,556,876 bp from pter      End:
130,576,606 bp from pter
Size:
19,731 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: FOLC_HUMAN, Q05932 (See protein sequence)
Recommended Name: Folylpolyglutamate synthase, mitochondrial precursor  
Size: 587 amino acids; 64609 Da
Cofactor: A monovalent cation. K(+) is most effective, followed by NH4(+) and Rb(+). Na(+), Li(+) and Cs(+) are
ineffective
Subunit: Monomer
Sequence caution: Sequence=AAA35852.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
Secondary accessions: B3KPW4 B7Z2Z3 F5H0K6 Q5JU19 Q5JU22 Q6P2P6
Alternative splicing, Alternative initiation: 4 isoforms:  Q05932-1   Q05932-2   Q05932-3   Q05932-4   (Produced by alternative splicing of isoform 1)

Explore the universe of human proteins at neXtProt for FPGS: NX_Q05932

Explore proteomics data for FPGS at MOPED

Post-translational modifications: 

  • Ubiquitination2 at Lys66, Lys107, Lys124, Lys154, Lys248
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for FPGS (Q05932) (see all 5)
     DHTSLLG  YFRFLTLMA  EKIAWQKGGIFK  VLVTGSLHLVGGVL 


    See FPGS Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (3 alternative transcripts): 
    NP_001018088.1  NP_001275732.1  NP_004948.4  

    ENSEMBL proteins: 
     ENSP00000362344   ENSP00000362325   ENSP00000362322   ENSP00000400007   ENSP00000406328  
     ENSP00000377309   ENSP00000362342  
    Reactome Protein details: Q05932

    FPGS Human Recombinant Protein Products:

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    Browse OriGene Protein Over-expression Lysates
    OriGene Custom MassSpec
    OriGene Custom Protein Services for FPGS
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    Novus Biologicals FPGS Protein
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for FPGS

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    LSBio Antibodies in human, mouse, rat for FPGS

    FPGS Assay Products:

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    Cloud-Clone Corp. CLIAs for FPGS


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    5 InterPro protein domains:
     IPR004101 Mur_ligase_C
     IPR023600 Folylpolyglutamate_synth_euk
     IPR013221 Mur_ligase_cen
     IPR001645 Folylpolyglutamate_synth
     IPR018109 Folylpolyglutamate_synth_CS

    Graphical View of Domain Structure for InterPro Entry Q05932

    ProtoNet protein and cluster: Q05932

    1 Blocks protein domain: IPB001645 Folylpolyglutamate synthetase

    UniProtKB/Swiss-Prot: FOLC_HUMAN, Q05932
    Similarity: Belongs to the folylpolyglutamate synthase family


    FPGS for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: FOLC_HUMAN, Q05932
    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
    Catalytic activity: ATP + tetrahydropteroyl-(gamma-Glu)(n) + L-glutamate = ADP + phosphate +
    tetrahydropteroyl-(gamma-Glu)(n+1)
    Enzyme regulation: Activated by 10 mM sodium bicarbonate
    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); KM=200 uM for MgATP (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=16 uM for 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=12 uM for PteGlu(4) (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=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=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=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=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=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=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=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=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=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=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=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=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=4.4 uM for aminopterin (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and
    2 mM L-glutamate); 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=52.6 uM for methotrexate (isoform 1, PubMed:17875718, at 37 degrees Celsius in the
    presence of 10 mM ATP and pH 8.5); 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=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=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=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=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=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=2068 uM for glutamic acid (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); 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); pH dependence: Optimum pH is 9.6 (isoform 2);

         Genatlas biochemistry entry for FPGS:
    folylpoly-gamma-glutamate synthase

         Enzyme Number (IUBMB): EC 6.3.2.171 2

         Gene Ontology (GO): 3 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004326tetrahydrofolylpolyglutamate synthase activity IEA--
    GO:0005524ATP binding IEA--
    GO:0016874ligase activity ----
         
    FPGS for ontologies           About GeneDecksing


    Phenotypes:
         1 GenomeRNAi human phenotype for FPGS:
     Increased viability after born 

         1 MGI mutant phenotype (inferred from 1 allele(MGI details for Fpgs):
     homeostasis/metabolism 

    FPGS for phenotypes           About GeneDecksing

    Animal Models:
       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for FPGS
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for FPGS

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for FPGS
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for FPGS

    miRNA
    Products:
        
    miRTarBase miRNAs that target FPGS:
    hsa-mir-222-3p (MIRT046816), hsa-mir-149-5p (MIRT045414), hsa-mir-124-3p (MIRT023124)

    Block miRNA regulation of human, mouse, rat FPGS using miScript Target Protectors
    5 qRT-PCR Assays for microRNAs that regulate FPGS:
    hsa-miR-124 hsa-miR-320e hsa-miR-765 hsa-miR-506 hsa-miR-30b*
    SwitchGear 3'UTR luciferase reporter plasmidFPGS 3' UTR sequence
    Inhib. RNA
    Products:
        
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    Predesigned siRNA for gene silencing in human, mouse, rat FPGS

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for FPGS

    Clone
    Products:
         
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    GenScript: all cDNA clones in your preferred vector (see all 2): FPGS (NM_004957)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for FPGS
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat FPGS

    Cell Line
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    In Situ Assay
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for FPGS


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    FOLC_HUMAN, Q05932: Isoform 1: Mitochondrion inner membrane. Mitochondrion matrix
    FOLC_HUMAN, Q05932: Isoform 2: Cytoplasm
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    mitochondrion5
    cytosol4
    lysosome1
    plasma membrane1

    Gene Ontology (GO): 5 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005737cytoplasm TAS1409616
    GO:0005739mitochondrion TAS7721888
    GO:0005743mitochondrial inner membrane IEA--
    GO:0005759mitochondrial matrix TAS--
    GO:0005829cytosol TAS--

    FPGS for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for FPGS About   (see all 7)  
    See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1Pyrimidine metabolism
    Fluoropyrimidine Activity0.69
    Fluoropyrimidine Pathway, Pharmacodynamics0.00
    2Metabolism
    Metabolism0.38
    Metabolic pathways0.38
    3Defective BTD causes biotidinase deficiency
    Defective BTD causes biotidinase deficiency1.00
    Metabolism of vitamins and cofactors1.00
    Defective AMN causes hereditary megaloblastic anemia 11.00
    Defective MMACHC causes methylmalonic aciduria and homocystinuria type cblC1.00
    Defective MMAA causes methylmalonic aciduria type cblA1.00
    Defective MUT causes methylmalonic aciduria mut type1.00
    Defective CD320 causes methylmalonic aciduria1.00
    Defects in cobalamin (B12) metabolism1.00
    4folate polyglutamylation
    folate polyglutamylation0.50
    5One carbon pool by folate
    Methotrexate Pathway (Cancer Cell), Pharmacodynamics0.35

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


    2 BioSystems Pathways for FPGS
        Fluoropyrimidine Activity
    folate polyglutamylation

    1 Reactome Pathway for FPGS
        Metabolism of folate and pterines

    2 PharmGKB Pathways for FPGS
        Fluoropyrimidine Pathway, Pharmacodynamics
    Methotrexate Pathway (Cancer Cell), Pharmacodynamics

    2 Kegg Pathways  (Kegg details for FPGS):
        Folate biosynthesis
    Metabolic pathways

    UniProtKB/Swiss-Prot: FOLC_HUMAN, Q05932
    Pathway: Cofactor biosynthesis; tetrahydrofolylpolyglutamate biosynthesis


    FPGS for pathways           About GeneDecksing

        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for FPGS
    Interactions:

        Search GeneGlobe Interaction Network for FPGS

    STRING Interaction Network Preview (showing 5 interactants - click image to see 23)

    Selected Interacting proteins for FPGS (Q059323 ENSP000003623444) via UniProtKB, MINT, STRING, and/or I2D (see all 69)

    InteractantInteraction Details
    GeneCardExternal ID(s)
    ENSG00000096171P266403I2D: score=1 
    ENSG00000224264P266403I2D: score=1 
    ENSG00000226589P266403I2D: score=1 
    ENSG00000231116P266403I2D: score=1 
    VARSP266403I2D: score=1 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 12):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001889liver development IEA--
    GO:0006139nucleobase-containing compound metabolic process TAS7721888
    GO:0006730one-carbon metabolic process IEA--
    GO:0006766vitamin metabolic process TAS--
    GO:0006767water-soluble vitamin metabolic process TAS--

    FPGS for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for FPGS (FOLC)

    10 HMDB Compounds for FPGS    About this table
    CompoundSynonyms CAS #PubMed Ids
    7,8-Dihydropteroic acid4-[[(2-amino-1,4,7,8-tetrahydro-4-oxo-6-pteridinyl)methyl]amino]-Benzoic acid (see all 12)2134-76-1--
    ADPadenosindiphosphorsaeure (see all 8)58-64-0--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--
    Dihydrofolic acid7,8-Dihydro-L-folic acid (see all 13)4033-27-6--
    FamotidineAmfamox (see all 83)76824-35-6--
    L-Glutamic acid(2S)-2-Aminopentanedioate (see all 49)56-86-0--
    PhosphateNFB Orthophosphate (see all 13)14265-44-2--
    Tetrahydrofolic acid(6S)-Tetrahydrofolate (see all 10)135-16-0--
    Tetrahydrofolyl-[Glu](2)THF-L-glutamate (see all 7)----
    Tetrahydrofolyl-[Glu](n)Tetrahydrofolyl-[Glu](n+1) (see all 5)----

    4 DrugBank Compounds for FPGS    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    L-Glutamic Acid(2S)-2-Aminopentanedioic acid (see all 15)56-86-0target--16686541 16990006
    MethotrexateAmethopterin (see all 12)59-05-2enzymesubstrate17586865
    Pralatrexate-- 146464-95-1enzymesubstrate23409799
    RaltitrexedZD-1694 (see all 2)112887-68-0targetantagonist11916544

    Selected Novoseek inferred chemical compound relationships for FPGS gene (see all 47)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    lometrexol 93.5 12 8869756 (2), 8937460 (1), 7565626 (1), 10598554 (1) (see all 8)
    glycinamide ribonucleotide 93.2 8 7565626 (1), 8027993 (1), 10598551 (1), 11469716 (1) (see all 7)
    tomudex 93.2 30 10477170 (5), 7646540 (3), 7513935 (2), 8255099 (1) (see all 14)
    1843u89 93.1 6 8764125 (4), 9816025 (1), 9242558 (1)
    thymidylate 92.2 52 10598551 (2), 9825730 (1), 10699949 (1), 16078850 (1) (see all 32)
    zd9331 91.7 5 9654109 (1), 8624289 (1), 12721264 (1), 9815766 (1)
    5-deazafolate 90.2 9 1578484 (2), 7565626 (1), 12408727 (1), 10479284 (1)
    dihydrofolate 89 32 1835598 (1), 8568827 (1), 9778690 (1), 10699949 (1) (see all 22)
    folate 89 283 8937460 (6), 8408018 (6), 8408019 (6), 18025275 (4) (see all 95)
    aminopterin 86.4 10 2007575 (1), 7506026 (1), 7565626 (1), 9744777 (1) (see all 6)

    1 PharmGKB related drug/compound annotation for FPGS gene    About this table
    Drug/compound PharmGKB Annotation
    methotrexateCA  



    FPGS for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for FPGS gene (3 alternative transcripts): 
    NM_001018078.2  NM_001288803.1  NM_004957.5  

    Unigene Cluster for FPGS:

    Folylpolyglutamate synthase
    Hs.335084  [show with all ESTs]
    Unigene Representative Sequence: NM_004957
    Selected Ensembl transcripts including schematic representations, and UCSC links where relevant (see all 21):
    ENST00000479147(uc004bsf.1) ENST00000479375 ENST00000373247 ENST00000488307
    ENST00000373228 ENST00000481552 ENST00000460181 ENST00000475765 ENST00000496586
    ENST00000373225(uc004bsi.1) ENST00000431857 ENST00000423577 ENST00000469310
    ENST00000497386 ENST00000488506 ENST00000489522 ENST00000467826 ENST00000473536

    Congresses - knowledge worth sharing:
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

    miRNA
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    Additional mRNA sequence: 

    AK056920.1 AK295309.1 AK315523.1 AY007210.1 AY007211.1 AY007212.1 BC007121.1 BC009901.2 
    BC064393.1 BT006639.1 M98045.1 

    18 DOTS entries:

    DT.100852186  DT.100030070  DT.92449883  DT.100640867  DT.100871571  DT.121190252  DT.95361622  DT.95361621 
    DT.40105946  DT.95361628  DT.95361629  DT.100659299  DT.121617824  DT.92449874  DT.92449886  DT.97764328 
    DT.97796004  DT.97854091 

    Selected AceView cDNA sequences (see all 407):

    BQ643944 BQ930310 CD619485 AI536944 BG014232 CR619508 BQ649035 AY007212 
    BE531124 BM975796 AI351075 AL526394 AI082295 BE207410 BC009901 BX436442 
    AI687246 M98045 AA298722 T25116 BM468258 BQ877844 BM449811 AY007210 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for FPGS (see all 15)    About this scheme

    ExUns: 1a · 1b · 1c ^ 2 ^ 3a · 3b ^ 4 ^ 5a · 5b ^ 6a · 6b · 6c · 6d ^ 7 ^ 8 ^ 9a · 9b ^ 10a · 10b ^ 11a · 11b ^ 12a · 12b · 12c ^ 13 ^ 14 ^
    SP1:                    -     -                       -     -                                         -     -                       -                           
    SP2:                    -     -                       -     -     -                                   -     -                       -                           
    SP3:                          -                       -     -                                         -     -                       -                           
    SP4:                                                  -     -     -                                   -     -           -     -     -                           
    SP5:                                                  -     -                                         -     -           -     -     -                           

    ExUns: 15 ^ 16a · 16b ^ 17
    SP1:                        
    SP2:                        
    SP3:                        
    SP4:                        
    SP5:                        


    ECgene alternative splicing isoforms for FPGS

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    FPGS expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    FPGS Expression
    About this image

    FPGS Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    FPGS Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.335084
        Custom PCR Arrays for FPGS
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of eukaryotes.

    Orthologs for FPGS gene from Selected species (see all 22)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Fpgs1 , 5 folylpolyglutamyl synthetase1, 5 82.51(n)1
    82.11(a)1
      2 (22.09 cM)5
    142871  NM_010236.21  NP_034366.21 
     326826095 
    chicken
    (Gallus gallus)
    Aves FPGS1 folylpolyglutamate synthase 71(n)
    69.48(a)
      417227  XM_003642277.2  XP_003642325.2 
    lizard
    (Anolis carolinensis)
    Reptilia FPGS6
    folylpolyglutamate synthase
    63(a)
    1 ↔ 1
    GL345096.1(3019-11417)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia fpgs1 folylpolyglutamate synthase 66.42(n)
    68.69(a)
      100125018  NM_001102943.1  NP_001096413.1 
    zebrafish
    (Danio rerio)
    Actinopterygii wufk51d092 Danio rerio cDNA clone MGC63807 IMAGE3815522, complete more 74.99(n)    BC058343.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta CG25431 , 3 folylpolyglutamate synthase3
    CG25431
    40(a)3
    54.03(n)1
    46.23(a)1
      322121  NM_132586.11  NP_572814.11 
    worm
    (Caenorhabditis elegans)
    Secernentea F25B5.6a3
    F25B5.61
    tetrahydrofolylpolyglutamate synthase3
    F25B5.61
    36(a)
    (best of 2)3
    47.07(n)1
    43.38(a)1
      III(6018152-6019942)3
    1758421  NM_065891.41  NP_498292.11 
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes MET7(YOR241W)4
    MET71
    Folylpolyglutamate synthetase, catalyzes extension more4
    MET71
    47.75(n)1
    45.89(a)1
      15(786995-788641)4
    8544151, 4  NP_014884.11, 4 
    thale cress
    (Arabidopsis thaliana)
    eudicotyledons DFB1 DFB 49.82(n)
    45.82(a)
      830484  NM_120680.3  NP_196217.2 
    rice
    (Oryza sativa)
    Liliopsida Os03g01111001 Os03g0111100 50(n)
    44.54(a)
      4331360  NM_001055256.1  NP_001048721.1 


    ENSEMBL Gene Tree for FPGS (if available)
    TreeFam Gene Tree for FPGS (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for FPGS (see all 390)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 9 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs109877411,2
    C--100179697(+) AACCCC/TGTCTC 1 -- us2k12Minor allele frequency- T:0.25NA 4
    rs1466727351,2
    --100179728(+) GCCGGC/GTGTGA 1 -- us2k10--------
    rs117900751,2
    C,F,A,H--100179833(+) CACTGT/CACTCC 1 -- us2k14Minor allele frequency- C:0.42NA 12
    rs285702991,2
    C,F--100180127(+) CTAAGA/TTGCAA 2 -- us2k15Minor allele frequency- T:0.21NA WA 126
    rs362047091,2
    C,F--100180208(+) CTATGG/TGACAC 2 -- us2k11Minor allele frequency- T:0.07EA 120
    rs1457697811,2
    C--100180317(+) TCATG-/ATTATTAT 2 -- us2k10--------
    rs1881751451,2
    --100180366(+) TGTCAA/CCCAGG 2 -- us2k10--------
    rs589962981,2
    C--100180472(+) AGGCGC/TCTGCT 2 -- us2k10--------
    rs597494071,2
    C--100180618(+) CACACC/TGGCTA 2 -- us2k10--------
    rs1144136261,2
    F--100180749(+) ACTGCG/ATCCAG 2 -- us2k11Minor allele frequency- A:0.09WA 118

    HapMap Linkage Disequilibrium report for FPGS (130556876 - 130576606 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 10 variations for FPGS:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv466576CNV Loss19166990
    dgv8288n71CNV Loss21882294
    nsv893868CNV Loss21882294
    nsv893865CNV Loss21882294
    nsv471323CNV Loss18288195
    dgv8287n71CNV Loss21882294
    nsv466575CNV Loss19166990
    nsv893874CNV Loss21882294
    nsv893859CNV Loss21882294
    nsv893860CNV Gain21882294

    Human Gene Mutation Database (HGMD): FPGS
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing FPGS
    DNA2.0 Custom Variant and Variant Library Synthesis for FPGS

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 136510    OMIM disorders: --

    Selected diseases for FPGS (see all 29):    
    About MalaCards
    childhood leukemia    malignant pleural mesothelioma    lymphoblastic leukemia    acute leukemia
    soft tissue sarcoma    follicular lymphoma    spina bifida    cleft lip
    diffuse large b-cell lymphoma    colorectal cancer    b-cell lymphomas    non-hodgkin lymphoma
    rheumatoid arthritis    hodgkin's lymphoma    sarcoma    leukemia
    blindness    psoriasis    arthritis    t-cell leukemia


    FPGS for disorders           About GeneDecksing

    Selected Novoseek inferred disease relationships for FPGS gene (see all 26)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    leukemia 58.3 32 19131550 (3), 8255099 (2), 11309345 (2), 2007575 (1) (see all 21)
    folate deficiency 50.9 4 15047700 (1), 18499665 (1), 8869756 (1), 18804693 (1)
    lymphoblastic leukemia acute 48.4 8 1435744 (2), 9654109 (1), 19131550 (1), 9242558 (1) (see all 6)
    t-all 47.6 9 16707018 (4), 10029597 (3), 11187907 (1)
    colorectal cancer 46.9 7 20037791 (2), 18418463 (1), 14676127 (1)
    tumors 43.1 78 8937460 (4), 14676127 (4), 1450491 (3), 18039426 (3) (see all 39)
    leukemia l1210 42.7 1 8605241 (1)
    leukemia nonlymphocytic acute 36.8 1 10777604 (1)
    colon cancer 34.4 10 15542523 (4), 20037791 (1), 12907242 (1), 14676127 (1)
    lymphoblastic leukemia acute childhood 31 1 20072153 (1)

    Genetic Association Database (GAD): FPGS
    Human Genome Epidemiology (HuGE) Navigator: FPGS (17 documents)

    Export disorders for FPGS gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for FPGS gene, integrated from 10 sources (see all 241):
    (articles sorted by number of sources associating them with FPGS)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Identification and characterization of genetic variation in the folylpolyglutamate synthase gene. (PubMed id 17875718)1, 2, 9 Leil T.A.... Adjei A.A. (Cancer Res. 2007)
    2. Purification and properties of human cytosolic folylpoly-gamma- glutamate synthetase and organization, localization, and differential splicing of its gene. (PubMed id 8662720)1, 2, 9 Chen L.... Shane B. (J. Biol. Chem. 1996)
    3. Upstream organization of and multiple transcripts from the human folylpoly-gamma-glutamate synthetase gene. (PubMed id 7721888)1, 2, 9 Freemantle S.J.... Moran R.G. (J. Biol. Chem. 1995)
    4. Concentration-dependent processivity of multiple glutamate ligations catalyzed by folylpoly-gamma-glutamate synthetase. (PubMed id 18672898)1, 2, 9 Tomsho J.W.... Coward J.K. (Biochemistry 2008)
    5. Exploratory analysis of four polymorphisms in human GGH and FPGS genes and their effect in methotrexate-treated rheumatoid arthritis patients. (PubMed id 17286537)1, 4, 9 van der Straaten R.J....Guchelaar H.J. (Pharmacogenomics 2007)
    6. Submitochondrial localization of the mitochondrial isoform of folylpolyglutamate synthetase in CCRF-CEM human T-lymphoblastic leukemia cells. (PubMed id 16169100)1, 2, 9 Nair J.R. and McGuire J.J. (Biochim. Biophys. Acta 2005)
    7. Expression cloning of a human cDNA encoding folylpoly(gamma- glutamate) synthetase and determination of its primary structure. (PubMed id 1409616)1, 2, 9 Garrow T.A.... Shane B. (Proc. Natl. Acad. Sci. U.S.A. 1992)
    8. Phase II trial of pemetrexed plus bevacizumab for second-line therapy of patients with advanced non-small-cell lung cancer: NCCTG and SWOG study N0426. (PubMed id 19841321)1, 4, 9 Adjei A.A....Zinner R.G. (J. Clin. Oncol. 2010)
    9. Genes involved with folate uptake and distribution and their association with colorectal cancer risk. (PubMed id 20037791)1, 4, 9 Figueiredo J.C....Haile R.W. (amp 2010)
    10. Outcomes of methotrexate therapy for psoriasis and relationship to genetic polymorphisms. (PubMed id 19016697)1, 4, 9 Warren R.B....Griffiths C.E. (Br. J. Dermatol. 2009)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 2356 HGNC: 3824 AceView: CDK9andFPGS Ensembl:ENSG00000136877 euGenes: HUgn2356
    ECgene: FPGS Kegg: 2356 H-InvDB: FPGS

    (According to HUGE)
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    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for FPGS Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for FPGS gene:
    Search GeneIP for patents involving FPGS

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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