FOLE_YEAST
ID FOLE_YEAST Reviewed; 548 AA.
AC Q08645; D6W2U3;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Folylpolyglutamate synthase;
DE EC=6.3.2.17;
DE AltName: Full=Folylpoly-gamma-glutamate synthetase;
DE Short=FPGS;
DE AltName: Full=Tetrahydrofolylpolyglutamate synthase;
DE Short=Tetrahydrofolate synthase;
GN Name=MET7; Synonyms=MET23; OrderedLocusNames=YOR241W; ORFNames=O5248;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 96604 / S288c / FY1679;
RX PubMed=8972580;
RX DOI=10.1002/(sici)1097-0061(199612)12:15<1575::aid-yea45>3.0.co;2-e;
RA Boyer J., Michaux G., Fairhead C., Gaillon L., Dujon B.;
RT "Sequence and analysis of a 26.9 kb fragment from chromosome XV of the
RT yeast Saccharomyces cerevisiae.";
RL Yeast 12:1575-1586(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169874;
RA Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J.,
RA Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A.,
RA Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B.,
RA Dang V.-D., de Haan M., Delius H., Durand P., Fairhead C., Feldmann H.,
RA Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E.,
RA Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U.,
RA Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B.,
RA Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A.,
RA Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C.,
RA Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G.,
RA Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B.,
RA Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B.,
RA Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F.,
RA Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E.,
RA Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I.,
RA Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H.,
RA Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XV.";
RL Nature 387:98-102(1997).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=17322287; DOI=10.1101/gr.6037607;
RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=10799479; DOI=10.1074/jbc.275.19.14056;
RA Cherest H., Thomas D., Surdin-Kerjan Y.;
RT "Polyglutamylation of folate coenzymes is necessary for methionine
RT biosynthesis and maintenance of intact mitochondrial genome in
RT Saccharomyces cerevisiae.";
RL J. Biol. Chem. 275:14056-14063(2000).
RN [6]
RP CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=10775416; DOI=10.1006/abbi.2000.1741;
RA DeSouza L., Shen Y., Bognar A.L.;
RT "Disruption of cytoplasmic and mitochondrial folylpolyglutamate synthetase
RT activity in Saccharomyces cerevisiae.";
RL Arch. Biochem. Biophys. 376:299-312(2000).
RN [7]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [8]
RP FUNCTION.
RX PubMed=15161972; DOI=10.1073/pnas.0401263101;
RA Askree S.H., Yehuda T., Smolikov S., Gurevich R., Hawk J., Coker C.,
RA Krauskopf A., Kupiec M., McEachern M.J.;
RT "A genome-wide screen for Saccharomyces cerevisiae deletion mutants that
RT affect telomere length.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:8658-8663(2004).
CC -!- FUNCTION: Catalyzes conversion of folates to polyglutamate derivatives
CC allowing concentration of folate compounds in the cell and the
CC intracellular retention of these cofactors, which are important
CC substrates for most of the folate-dependent enzymes that are involved
CC in one-carbon transfer reactions involved in purine, pyrimidine and
CC amino acid synthesis. Required for methionine synthesis and maintenance
CC of intact mitochondrial DNA. Involved in telomere maintenance.
CC {ECO:0000269|PubMed:10799479, ECO:0000269|PubMed:15161972}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-5,6,7,8-tetrahydrofolyl-(gamma-L-Glu)(n) + ATP + L-
CC glutamate = (6S)-5,6,7,8-tetrahydrofolyl-(gamma-L-Glu)(n+1) + ADP +
CC H(+) + phosphate; Xref=Rhea:RHEA:10580, Rhea:RHEA-COMP:14738,
CC Rhea:RHEA-COMP:14740, ChEBI:CHEBI:15378, ChEBI:CHEBI:29985,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:141005,
CC ChEBI:CHEBI:456216; EC=6.3.2.17;
CC Evidence={ECO:0000269|PubMed:10775416, ECO:0000269|PubMed:10799479};
CC -!- COFACTOR:
CC Name=a monovalent cation; Xref=ChEBI:CHEBI:60242;
CC Evidence={ECO:0000250};
CC Note=A monovalent cation. {ECO:0000250};
CC -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolylpolyglutamate
CC biosynthesis.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:10775416}.
CC Mitochondrion inner membrane {ECO:0000250}. Mitochondrion matrix
CC {ECO:0000250}. Cytoplasm {ECO:0000269|PubMed:10775416}.
CC -!- DISRUPTION PHENOTYPE: Methionine auxotroph. Undetectable levels of
CC folylpolyglutamate synthase activity. Increased rate of loss of
CC mitochondrial DNA. Respiration-deficient. MET7 and FOL3 double mutant
CC cells are not viable even in the presence of methionine and folinic
CC acid. MET7, FOL3 and TUP1 triple disruption mutant is able to germinate
CC on YPGA medium containing thymidylate and to grow although poorly on
CC synthetic medium containing methionine, adenine and thymidylate.
CC Adenine and thymidine auxotroph when grown in the presence of
CC sulfanilamide. Becomes petite under normal growth conditions but can be
CC maintained with a grande phenotype if the strain is TUP1 and all media
CC are supplemented with dTMP. MET7 and GLY1 double mutant is auxotrophic
CC for glycine when grown on glucose but prototrophic when grown on
CC glycerol. MET7 and SER1 double mutant cannot use glycine to suppress
CC serine auxotrophy. MET7 and SHM2 double mutant is nonviable.
CC {ECO:0000269|PubMed:10775416, ECO:0000269|PubMed:10799479}.
CC -!- MISCELLANEOUS: Present with 7080 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the folylpolyglutamate synthase family.
CC {ECO:0000305}.
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DR EMBL; Z75149; CAA99462.1; -; Genomic_DNA.
DR EMBL; AY692818; AAT92837.1; -; Genomic_DNA.
DR EMBL; BK006948; DAA11009.1; -; Genomic_DNA.
DR PIR; S67134; S67134.
DR RefSeq; NP_014884.1; NM_001183660.1.
DR AlphaFoldDB; Q08645; -.
DR SMR; Q08645; -.
DR BioGRID; 34632; 255.
DR DIP; DIP-4986N; -.
DR IntAct; Q08645; 10.
DR STRING; 4932.YOR241W; -.
DR iPTMnet; Q08645; -.
DR MaxQB; Q08645; -.
DR PaxDb; Q08645; -.
DR PRIDE; Q08645; -.
DR TopDownProteomics; Q08645; -.
DR EnsemblFungi; YOR241W_mRNA; YOR241W; YOR241W.
DR GeneID; 854415; -.
DR KEGG; sce:YOR241W; -.
DR SGD; S000005767; MET7.
DR VEuPathDB; FungiDB:YOR241W; -.
DR eggNOG; KOG2525; Eukaryota.
DR GeneTree; ENSGT00390000016526; -.
DR HOGENOM; CLU_015869_0_1_1; -.
DR InParanoid; Q08645; -.
DR OMA; FFFEVWD; -.
DR BioCyc; YEAST:YOR241W-MON; -.
DR Reactome; R-SCE-196757; Metabolism of folate and pterines.
DR UniPathway; UPA00850; -.
DR PRO; PR:Q08645; -.
DR Proteomes; UP000002311; Chromosome XV.
DR RNAct; Q08645; protein.
DR GO; GO:0005737; C:cytoplasm; IDA:SGD.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; HDA:SGD.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:SGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004326; F:tetrahydrofolylpolyglutamate synthase activity; IDA:SGD.
DR GO; GO:0009396; P:folic acid-containing compound biosynthetic process; IBA:GO_Central.
DR GO; GO:0006730; P:one-carbon metabolic process; IMP:SGD.
DR GO; GO:0046901; P:tetrahydrofolylpolyglutamate biosynthetic process; IBA:GO_Central.
DR Gene3D; 3.40.1190.10; -; 1.
DR Gene3D; 3.90.190.20; -; 1.
DR InterPro; IPR001645; Folylpolyglutamate_synth.
DR InterPro; IPR018109; Folylpolyglutamate_synth_CS.
DR InterPro; IPR023600; Folylpolyglutamate_synth_euk.
DR InterPro; IPR036565; Mur-like_cat_sf.
DR InterPro; IPR036615; Mur_ligase_C_dom_sf.
DR PANTHER; PTHR11136; PTHR11136; 1.
DR PANTHER; PTHR11136:SF5; PTHR11136:SF5; 1.
DR PIRSF; PIRSF038895; FPGS; 1.
DR SUPFAM; SSF53244; SSF53244; 1.
DR SUPFAM; SSF53623; SSF53623; 1.
DR TIGRFAMs; TIGR01499; folC; 1.
DR PROSITE; PS01011; FOLYLPOLYGLU_SYNT_1; 1.
DR PROSITE; PS01012; FOLYLPOLYGLU_SYNT_2; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cytoplasm; Ligase; Magnesium; Membrane; Metal-binding;
KW Mitochondrion; Mitochondrion inner membrane; Nucleotide-binding;
KW One-carbon metabolism; Reference proteome.
FT CHAIN 1..548
FT /note="Folylpolyglutamate synthase"
FT /id="PRO_0000168312"
FT BINDING 130..133
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 157
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 234
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 262
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 382
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 396
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P08192"
SQ SEQUENCE 548 AA; 62151 MW; F36811FB4B7E9305 CRC64;
MHKGKKNYPN LITSFRMNLK KIILNHDRFS HPERWKTNAL LRFTFVYIKF LFDLMIIKNP
LRMVGKTYRD AVTALNSLQS NYANIMAIRQ TGDRKNTMTL LEMHEWSRRI GYSASDFNKL
NIVHITGTKG KGSTAAFTSS ILGQYKEQLP RIGLYTSPHL KSVRERIRIN GEPISEEKFA
KYFFEVWDRL DSTTSSLDKF PHMIPGSKPG YFKFLTLLSF HTFIQEDCKS CVYEVGVGGE
LDSTNIIEKP IVCGVTLLGI DHTFMLGDTI EEIAWNKGGI FKSGAPAFTV EKQPPQGLTI
LKERAEERKT TLTEVPPFKQ LENVKLGIAG EFQKSNASLA VMLASEILHT SNILEEKIKC
SSNASIPEKF IIGLQNTKWE GRCQVLEKGK NVWYIDGAHT KDSMVAASTW FRDMVRLSKR
KKILLFNQQS RDANALVNNL YSSVSPEITF DDVIFTTNVT WKSGSYSADL VSMNTSQEDV
EKLKVQESLV KNWNKIDDNR AKTHVTASIE EANELIETLY DEPADIFVTG SLHLVGGLLV
VFDRIDVK
