LOCUS       NM_004957               2284 bp    mRNA    linear   PRI 21-SEP-2024
DEFINITION  Homo sapiens folylpolyglutamate synthase (FPGS), transcript variant
            1, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_004957
VERSION     NM_004957.6
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 2284)
  AUTHORS   Mitarai,Y., Tanino,R., Nakashima,K., Hotta,T., Isobe,T. and
            Tsubata,Y.
  TITLE     Effects of single nucleotide polymorphisms of the
            folylpolyglutamate synthase gene on pemetrexed
            administration-induced nephropathy
  JOURNAL   Br J Clin Pharmacol 89 (12), 3551-3560 (2023)
   PUBMED   37452621
  REMARK    GeneRIF: Effects of single nucleotide polymorphisms of the
            folylpolyglutamate synthase gene on pemetrexed
            administration-induced nephropathy.
REFERENCE   2  (bases 1 to 2284)
  AUTHORS   Morgenstern,M., Peikert,C.D., Lubbert,P., Suppanz,I., Klemm,C.,
            Alka,O., Steiert,C., Naumenko,N., Schendzielorz,A., Melchionda,L.,
            Muhlhauser,W.W.D., Knapp,B., Busch,J.D., Stiller,S.B.,
            Dannenmaier,S., Lindau,C., Licheva,M., Eickhorst,C., Galbusera,R.,
            Zerbes,R.M., Ryan,M.T., Kraft,C., Kozjak-Pavlovic,V., Drepper,F.,
            Dennerlein,S., Oeljeklaus,S., Pfanner,N., Wiedemann,N. and
            Warscheid,B.
  TITLE     Quantitative high-confidence human mitochondrial proteome and its
            dynamics in cellular context
  JOURNAL   Cell Metab 33 (12), 2464-2483 (2021)
   PUBMED   34800366
REFERENCE   3  (bases 1 to 2284)
  AUTHORS   Fernandes,M.R., Rodrigues,J.C.G., Dobbin,E.A.F., Pastana,L.F., da
            Costa,D.F., Barra,W.F., Modesto,A.A.C., de Assumpcao,P.B., da Costa
            Silva,A.L., Dos Santos,S.E.B., Burbano,R.M.R., de Assumpcao,P.P.
            and Dos Santos,N.P.C.
  TITLE     Influence of FPGS, ABCC4, SLC29A1, and MTHFR genes on the
            pharmacogenomics of fluoropyrimidines in patients with
            gastrointestinal cancer from the Brazilian Amazon
  JOURNAL   Cancer Chemother Pharmacol 88 (5), 837-844 (2021)
   PUBMED   34331561
  REMARK    GeneRIF: Influence of FPGS, ABCC4, SLC29A1, and MTHFR genes on the
            pharmacogenomics of fluoropyrimidines in patients with
            gastrointestinal cancer from the Brazilian Amazon.
REFERENCE   4  (bases 1 to 2284)
  AUTHORS   Muller,I.B., Lin,M., Lems,W.F., Ter Wee,M.M., Wojtuszkiewicz,A.,
            Nurmohamed,M.T., Cloos,J., Assaraf,Y.G., Jansen,G. and de Jonge,R.
  TITLE     Association of altered folylpolyglutamate synthetase pre-mRNA
            splicing with methotrexate unresponsiveness in early rheumatoid
            arthritis
  JOURNAL   Rheumatology (Oxford) 60 (3), 1273-1281 (2021)
   PUBMED   32940699
  REMARK    GeneRIF: Association of altered folylpolyglutamate synthetase
            pre-mRNA splicing with methotrexate unresponsiveness in early
            rheumatoid arthritis.
REFERENCE   5  (bases 1 to 2284)
  AUTHORS   Yu,S.L., Zhang,H., Ho,B.C., Yu,C.H., Chang,C.C., Hsu,Y.C., Ni,Y.L.,
            Lin,K.H., Jou,S.T., Lu,M.Y., Chen,S.H., Wu,K.H., Wang,S.C.,
            Chang,H.H., Pui,C.H., Yang,J.J., Zhang,J., Lin,D.T., Lin,S.W.,
            Ma,X. and Yang,Y.L.
  TITLE     FPGS relapse-specific mutations in relapsed childhood acute
            lymphoblastic leukemia
  JOURNAL   Sci Rep 10 (1), 12074 (2020)
   PUBMED   32694622
  REMARK    GeneRIF: FPGS relapse-specific mutations in relapsed childhood
            acute lymphoblastic leukemia.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 2284)
  AUTHORS   Freemantle,S.J., Taylor,S.M., Krystal,G. and Moran,R.G.
  TITLE     Upstream organization of and multiple transcripts from the human
            folylpoly-gamma-glutamate synthetase gene
  JOURNAL   J Biol Chem 270 (16), 9579-9584 (1995)
   PUBMED   7721888
REFERENCE   7  (bases 1 to 2284)
  AUTHORS   Garrow,T.A., Admon,A. and Shane,B.
  TITLE     Expression cloning of a human cDNA encoding
            folylpoly(gamma-glutamate) synthetase and determination of its
            primary structure
  JOURNAL   Proc Natl Acad Sci U S A 89 (19), 9151-9155 (1992)
   PUBMED   1409616
REFERENCE   8  (bases 1 to 2284)
  AUTHORS   Clarke,L. and Waxman,D.J.
  TITLE     Human liver folylpolyglutamate synthetase: biochemical
            characterization and interactions with folates and folate
            antagonists
  JOURNAL   Arch Biochem Biophys 256 (2), 585-596 (1987)
   PUBMED   3619447
REFERENCE   9  (bases 1 to 2284)
  AUTHORS   Cichowicz,D.J. and Shane,B.
  TITLE     Mammalian folylpoly-gamma-glutamate synthetase. 1. Purification and
            general properties of the hog liver enzyme
  JOURNAL   Biochemistry 26 (2), 504-512 (1987)
   PUBMED   3828320
REFERENCE   10 (bases 1 to 2284)
  AUTHORS   Jones,C., Kao,F.T. and Taylor,R.T.
  TITLE     Chromosomal assignment of the gene for folylpolyglutamate
            synthetase to human chromosome 9
  JOURNAL   Cytogenet Cell Genet 28 (3), 181-194 (1980)
   PUBMED   6934068
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DC365273.1, BC064393.1,
            BC007121.1 and CB854085.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 17, 2019 this sequence version replaced NM_004957.5.
            
            Summary: 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].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes isoform (a). This variant has two
            alternative translational start codons in the same reading frame
            which encode either a longer, signal-containing mitochondrial
            protein or a shorter, signal-less cytosolic protein.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: BC064393.1, M98045.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1968189
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000373247.7/
                                                  ENSP00000362344.2
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-146               DC365273.1         25-170
            147-1508            BC064393.1         133-1494
            1509-1998           BC007121.1         1464-1953
            1999-2284           CB854085.1         284-569
FEATURES             Location/Qualifiers
     source          1..2284
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="9"
                     /map="9q34.11"
     gene            1..2284
                     /gene="FPGS"
                     /note="folylpolyglutamate synthase"
                     /db_xref="GeneID:2356"
                     /db_xref="HGNC:HGNC:3824"
                     /db_xref="MIM:136510"
     exon            1..181
                     /gene="FPGS"
                     /inference="alignment:Splign:2.1.0"
     CDS             44..1807
                     /gene="FPGS"
                     /EC_number="6.3.2.17"
                     /note="isoform a precursor is encoded by transcript
                     variant 1; tetrahydrofolate synthase;
                     folylpoly-gamma-glutamate synthetase;
                     tetrahydrofolylpolyglutamate synthase; folylpolyglutamate
                     synthase, mitochondrial"
                     /codon_start=1
                     /product="folylpolyglutamate synthase, mitochondrial
                     isoform a precursor"
                     /protein_id="NP_004948.4"
                     /db_xref="CCDS:CCDS35148.1"
                     /db_xref="GeneID:2356"
                     /db_xref="HGNC:HGNC:3824"
                     /db_xref="MIM:136510"
                     /translation="MSRARSHLRAALFLAAASARGITTQVAARRGLSAWPVPQEPSME
                     YQDAVRMLNTLQTNAGYLEQVKRQRGDPQTQLEAMELYLARSGLQVEDLDRLNIIHVT
                     GTKGKGSTCAFTECILRSYGLKTGFFSSPHLVQVRERIRINGQPISPELFTKYFWRLY
                     HRLEETKDGSCVSMPPYFRFLTLMAFHVFLQEKVDLAVVEVGIGGAYDCTNIIRKPVV
                     CGVSSLGIDHTSLLGDTVEKIAWQKGGIFKQGVPAFTVLQPEGPLAVLRDRAQQISCP
                     LYLCPMLEALEEGGPPLTLGLEGEHQRSNAALALQLAHCWLQRQDRHGAGEPKASRPG
                     LLWQLPLAPVFQPTSHMRLGLRNTEWPGRTQVLRRGPLTWYLDGAHTASSAQACVRWF
                     RQALQGRERPSGGPEVRVLLFNATGDRDPAALLKLLQPCQFDYAVFCPNLTEVSSTGN
                     ADQQNFTVTLDQVLLRCLEHQQHWNHLDEEQASPDLWSAPSPEPGGSASLLLAPHPPH
                     TCSASSLVFSCISHALQWISQGRDPIFQPPSPPKGLLTHPVAHSGASILREAAAIHVL
                     VTGSLHLVGGVLKLLEPALSQ"
     exon            182..310
                     /gene="FPGS"
                     /inference="alignment:Splign:2.1.0"
     exon            311..364
                     /gene="FPGS"
                     /inference="alignment:Splign:2.1.0"
     exon            365..429
                     /gene="FPGS"
                     /inference="alignment:Splign:2.1.0"
     exon            430..544
                     /gene="FPGS"
                     /inference="alignment:Splign:2.1.0"
     exon            545..622
                     /gene="FPGS"
                     /inference="alignment:Splign:2.1.0"
     exon            623..684
                     /gene="FPGS"
                     /inference="alignment:Splign:2.1.0"
     exon            685..787
                     /gene="FPGS"
                     /inference="alignment:Splign:2.1.0"
     exon            788..865
                     /gene="FPGS"
                     /inference="alignment:Splign:2.1.0"
     exon            866..1013
                     /gene="FPGS"
                     /inference="alignment:Splign:2.1.0"
     exon            1014..1103
                     /gene="FPGS"
                     /inference="alignment:Splign:2.1.0"
     exon            1104..1254
                     /gene="FPGS"
                     /inference="alignment:Splign:2.1.0"
     exon            1255..1330
                     /gene="FPGS"
                     /inference="alignment:Splign:2.1.0"
     exon            1331..1397
                     /gene="FPGS"
                     /inference="alignment:Splign:2.1.0"
     exon            1398..2284
                     /gene="FPGS"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2240..2245
                     /regulatory_class="polyA_signal_sequence"
                     /gene="FPGS"
                     /note="hexamer: ATTAAA"
     regulatory      2260..2265
                     /regulatory_class="polyA_signal_sequence"
                     /gene="FPGS"
                     /note="hexamer: AAGAAA"
     polyA_site      2265
                     /gene="FPGS"
                     /note="major polyA site"
     polyA_site      2284
                     /gene="FPGS"
ORIGIN      
        1 gtctcccgcc cgggcctaga gcgctgccgg gggcgccggg actatgtcgc gggcgcggag
       61 ccacctgcgc gccgctctat tcctggcagc ggcgtctgcg cgcggcataa cgacccaggt
      121 cgcggcgcgg cggggcttga gcgcgtggcc ggtgccgcag gagccgagca tggagtacca
      181 ggatgccgtg cgcatgctca ataccctgca gaccaatgcc ggctacctgg agcaggtgaa
      241 gcgccagcgg ggtgaccctc agacacagtt ggaagccatg gaactgtacc tggcacggag
      301 tgggctgcag gtggaggact tggaccggct gaacatcatc cacgtcactg ggacgaaggg
      361 gaagggctcc acctgtgcct tcacggaatg tatcctccga agctatggcc tgaagacggg
      421 attctttagc tctccccacc tggtgcaggt tcgggagcgg atccgcatca atgggcagcc
      481 catcagtcct gagctcttca ccaagtactt ctggcgcctc taccaccggc tggaggagac
      541 caaggatggc agctgtgtct ccatgccccc ctacttccgc ttcctgacac tcatggcctt
      601 ccacgtcttc ctccaagaga aggtggacct ggcagtggtg gaggtgggca ttggcggggc
      661 ttatgactgc accaacatca tcaggaagcc tgtggtgtgc ggagtctcct ctcttggcat
      721 cgaccacacc agcctcctgg gggatacggt ggagaagatc gcatggcaga aagggggcat
      781 ctttaagcaa ggtgtccctg ccttcactgt gctccaacct gaaggtcccc tggcagtgct
      841 gagggaccga gcccagcaga tctcatgtcc tctatacctg tgtccgatgc tggaggccct
      901 cgaggaaggg gggccgccgc tgaccctggg cctggagggg gagcaccagc ggtccaacgc
      961 cgccttggcc ttgcagctgg cccactgctg gctgcagcgg caggaccgcc atggtgctgg
     1021 ggagccaaag gcatccaggc cagggctcct gtggcagctg cccctggcac ctgtgttcca
     1081 gcccacatcc cacatgcggc tcgggcttcg gaacacggag tggccgggcc ggacgcaggt
     1141 gctgcggcgc gggcccctca cctggtacct ggacggtgcg cacaccgcca gcagcgcgca
     1201 ggcctgcgtg cgctggttcc gccaggcgct gcagggccgc gagaggccga gcggtggccc
     1261 cgaggttcga gtcttgctct tcaatgctac cggggaccgg gacccggcgg ccctgctgaa
     1321 gctgctgcag ccctgccagt ttgactatgc cgtcttctgc cctaacctga cagaggtgtc
     1381 atccacaggc aacgcagacc aacagaactt cacagtgaca ctggaccagg tcctgctccg
     1441 ctgcctggaa caccagcagc actggaacca cctggacgaa gagcaggcca gcccggacct
     1501 ctggagtgcc cccagcccag agcccggtgg gtccgcatcc ctgcttctgg cgccccaccc
     1561 accccacacc tgcagtgcca gctccctcgt cttcagctgc atttcacatg ccttgcaatg
     1621 gatcagccaa ggccgagacc ccatcttcca gccacctagt cccccaaagg gcctcctcac
     1681 ccaccctgtg gctcacagtg gggccagcat actccgtgag gctgctgcca tccatgtgct
     1741 agtcactggc agcctgcacc tggtgggtgg tgtcctgaag ctgctggagc ccgcactgtc
     1801 ccagtagcca aggcccgggg ttggaggtgg gagcttccca cacctgcctg cgttctcccc
     1861 atgaacttac atactaggtg ccttttgttt ttggctttcc tggttctgtc tagactggcc
     1921 taggggccag ggctttggga tgggaggccg ggagaggatg tcttttttaa ggctctgtgc
     1981 cttggtctct ccttcctctt ggctgagata gcagaggggc tccccgggtc tctcactgtt
     2041 gcagtggcct ggccgttcag cctgtctccc ccaacacccc gcctgcctcc tggctcaggc
     2101 ccagcttatt gtgtgcgctg cctggccagg ccctgggtct tgccatgtgc tgggtggtag
     2161 atttcctcct cccagtgcct tctgggaagg gagagggcct ctgcctggga cactgcggga
     2221 cagagggtgg ctggagtgaa ttaaagcctt tgttttttaa agaaatggca aagccttcga
     2281 ctga
//
