FOLE_NEUCR
ID FOLE_NEUCR Reviewed; 528 AA.
AC O13492; Q7RW09; V5IRB3;
DT 16-MAY-2003, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2005, sequence version 2.
DT 03-AUG-2022, entry version 126.
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=met-6; ORFNames=B13C5.220, NCU00892;
OS Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 /
OS FGSC 987).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Sordariales; Sordariaceae; Neurospora.
OX NCBI_TaxID=367110;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], DEVELOPMENTAL STAGE, VARIANTS GLN-32;
RP SER-107 AND ILE-108, AND MUTAGENESIS OF SER-134.
RC STRAIN=ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987;
RX PubMed=9887523; DOI=10.1016/s0031-9422(98)00317-3;
RA Atkinson I.J., Nargang F.E., Cossins E.A.;
RT "Folylpolyglutamate synthesis in Neurospora crassa: primary structure of
RT the folylpolyglutamate synthetase gene and elucidation of the met-6
RT mutation.";
RL Phytochemistry 49:2221-2232(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987;
RX PubMed=12655011; DOI=10.1093/nar/gkg293;
RA Mannhaupt G., Montrone C., Haase D., Mewes H.-W., Aign V., Hoheisel J.D.,
RA Fartmann B., Nyakatura G., Kempken F., Maier J., Schulte U.;
RT "What's in the genome of a filamentous fungus? Analysis of the Neurospora
RT genome sequence.";
RL Nucleic Acids Res. 31:1944-1954(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987;
RX PubMed=12712197; DOI=10.1038/nature01554;
RA Galagan J.E., Calvo S.E., Borkovich K.A., Selker E.U., Read N.D.,
RA Jaffe D.B., FitzHugh W., Ma L.-J., Smirnov S., Purcell S., Rehman B.,
RA Elkins T., Engels R., Wang S., Nielsen C.B., Butler J., Endrizzi M.,
RA Qui D., Ianakiev P., Bell-Pedersen D., Nelson M.A., Werner-Washburne M.,
RA Selitrennikoff C.P., Kinsey J.A., Braun E.L., Zelter A., Schulte U.,
RA Kothe G.O., Jedd G., Mewes H.-W., Staben C., Marcotte E., Greenberg D.,
RA Roy A., Foley K., Naylor J., Stange-Thomann N., Barrett R., Gnerre S.,
RA Kamal M., Kamvysselis M., Mauceli E.W., Bielke C., Rudd S., Frishman D.,
RA Krystofova S., Rasmussen C., Metzenberg R.L., Perkins D.D., Kroken S.,
RA Cogoni C., Macino G., Catcheside D.E.A., Li W., Pratt R.J., Osmani S.A.,
RA DeSouza C.P.C., Glass N.L., Orbach M.J., Berglund J.A., Voelker R.,
RA Yarden O., Plamann M., Seiler S., Dunlap J.C., Radford A., Aramayo R.,
RA Natvig D.O., Alex L.A., Mannhaupt G., Ebbole D.J., Freitag M., Paulsen I.,
RA Sachs M.S., Lander E.S., Nusbaum C., Birren B.W.;
RT "The genome sequence of the filamentous fungus Neurospora crassa.";
RL Nature 422:859-868(2003).
RN [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=7766162; DOI=10.1016/0031-9422(94)00713-4;
RA Atkinson I.J., Nargang F.E., Cossins E.A.;
RT "Folylpolyglutamate synthesis in Neurospora crassa: transformation of
RT polyglutamate-deficient mutants.";
RL Phytochemistry 38:603-608(1995).
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. {ECO:0000269|PubMed:7766162}.
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:7766162};
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 inner membrane {ECO:0000250}.
CC Mitochondrion matrix {ECO:0000250}. Cytoplasm {ECO:0000250}.
CC -!- DEVELOPMENTAL STAGE: Higher transcript levels are detected in freshly
CC germinated mycelium, with less expression seen in ungerminated conidia
CC and cultures near stationary phase. {ECO:0000269|PubMed:9887523}.
CC -!- SIMILARITY: Belongs to the folylpolyglutamate synthase family.
CC {ECO:0000305}.
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DR EMBL; AF005040; AAB61730.1; -; Genomic_DNA.
DR EMBL; BX842682; CAE82006.1; -; Genomic_DNA.
DR EMBL; CM002236; ESA44238.1; -; Genomic_DNA.
DR EMBL; CM002236; ESA44239.1; -; Genomic_DNA.
DR PIR; T47217; T47217.
DR RefSeq; XP_011392846.1; XM_011394544.1.
DR RefSeq; XP_011392847.1; XM_011394545.1.
DR AlphaFoldDB; O13492; -.
DR SMR; O13492; -.
DR STRING; 5141.EFNCRP00000000529; -.
DR EnsemblFungi; ESA44238; ESA44238; NCU00892.
DR EnsemblFungi; ESA44239; ESA44239; NCU00892.
DR GeneID; 3880932; -.
DR KEGG; ncr:NCU00892; -.
DR VEuPathDB; FungiDB:NCU00892; -.
DR HOGENOM; CLU_015869_0_1_1; -.
DR InParanoid; O13492; -.
DR UniPathway; UPA00850; -.
DR Proteomes; UP000001805; Chromosome 1, Linkage Group I.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
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; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0009396; P:folic acid-containing compound biosynthetic process; IBA:GO_Central.
DR GO; GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-KW.
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 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..528
FT /note="Folylpolyglutamate synthase"
FT /id="PRO_0000168310"
FT BINDING 104..107
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 134
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 208
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 236
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 351
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 365
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT VARIANT 32
FT /note="K -> Q"
FT /evidence="ECO:0000269|PubMed:9887523"
FT VARIANT 107
FT /note="G -> S"
FT /evidence="ECO:0000269|PubMed:9887523"
FT VARIANT 108
FT /note="T -> I"
FT /evidence="ECO:0000269|PubMed:9887523"
FT MUTAGEN 134
FT /note="S->P: In met-6; auxotrophic to methionine."
FT /evidence="ECO:0000269|PubMed:9887523"
FT CONFLICT 288
FT /note="L -> P (in Ref. 1; AAB61730)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 528 AA; 58525 MW; 8BB0D505041D30CB CRC64;
MHHVLRPIAF RLALVSPLRS LTITHHHLFF TKRTMASSAR TYNDAIDALN SLQTPFAVIE
ARRKAGIRPD AHSVKEMRAY LARIGYSSQD LDRLNIVHVA GTKGKGGTCA FVDSILTRHQ
RTHGIPRRIG LFTSPHLIAV RERIRIDSKP ISEELFARYF FEVWDRLETS QLAKDEVELG
SKPIYARYLT LMSYHVYLSE GVDVAIYETG IGGEYDATNV VDRPVVSGIS TLGIDHVFVL
GDTVDKIAWH KAGIMKTGSP AFTIEQVPSA TQVLKDRAVE KGVDLKILDV DPRLNGVKIR
PDAVFQKKNA TLAIALAETA LKKLDPSFKP GTDSLSPEFV QGLEQVVWRG RCEVKEEDQA
VWHLDGAHTV DSLKVAGRWF VEECVKKAKG GPKVLIFNQQ GRSEAVDFLD GLCNTVKSAD
PEGTGFSHVI FCTNVTYATT GYKKDFVNHQ YNPKDIENMT QQRVFAERWS TLDPSANVML
IPTIEEAINK ARSLVDTTEG EQKVQALITG SLHLVGGALG ILEKADAL
