FOLC_CAEEL
ID FOLC_CAEEL Reviewed; 510 AA.
AC Q09509; Q5DX42; Q95QJ2;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Putative 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 ORFNames=F25B5.6;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], ALTERNATIVE INITIATION, AND
RP ALTERNATIVE SPLICING.
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
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:0000250}.
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 -!- 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
CC {ECO:0000250|UniProtKB:Q05932}. Mitochondrion matrix
CC {ECO:0000250|UniProtKB:Q05932}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q05932}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=3;
CC Name=a;
CC IsoId=Q09509-1; Sequence=Displayed;
CC Name=b;
CC IsoId=Q09509-2; Sequence=VSP_041964;
CC Name=c;
CC IsoId=Q09509-3; Sequence=VSP_041963;
CC -!- MISCELLANEOUS: [Isoform b]: Produced by alternative splicing.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform c]: Produced by alternative initiation at Met-
CC 27 of isoform a. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the folylpolyglutamate synthase family.
CC {ECO:0000305}.
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DR EMBL; FO081045; CCD68782.1; -; Genomic_DNA.
DR EMBL; FO081045; CCD68783.1; -; Genomic_DNA.
DR EMBL; FO081045; CCD68784.1; -; Genomic_DNA.
DR PIR; T16146; T16146.
DR RefSeq; NP_001022548.1; NM_001027377.2. [Q09509-3]
DR RefSeq; NP_498291.1; NM_065890.1. [Q09509-2]
DR RefSeq; NP_498292.1; NM_065891.4.
DR AlphaFoldDB; Q09509; -.
DR SMR; Q09509; -.
DR BioGRID; 41063; 10.
DR IntAct; Q09509; 1.
DR STRING; 6239.F25B5.6b; -.
DR EPD; Q09509; -.
DR PaxDb; Q09509; -.
DR PeptideAtlas; Q09509; -.
DR EnsemblMetazoa; F25B5.6a.1; F25B5.6a.1; WBGene00017777. [Q09509-1]
DR EnsemblMetazoa; F25B5.6b.1; F25B5.6b.1; WBGene00017777. [Q09509-2]
DR EnsemblMetazoa; F25B5.6c.1; F25B5.6c.1; WBGene00017777. [Q09509-3]
DR GeneID; 175842; -.
DR KEGG; cel:CELE_F25B5.6; -.
DR UCSC; F25B5.6a; c. elegans.
DR CTD; 175842; -.
DR WormBase; F25B5.6a; CE01923; WBGene00017777; -. [Q09509-1]
DR WormBase; F25B5.6b; CE29283; WBGene00017777; -. [Q09509-2]
DR WormBase; F25B5.6c; CE37764; WBGene00017777; -. [Q09509-3]
DR eggNOG; KOG2525; Eukaryota.
DR GeneTree; ENSGT00390000016526; -.
DR InParanoid; Q09509; -.
DR OMA; FFFEVWD; -.
DR OrthoDB; 840266at2759; -.
DR Reactome; R-CEL-196757; Metabolism of folate and pterines.
DR UniPathway; UPA00850; -.
DR PRO; PR:Q09509; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00017777; Expressed in germ line (C elegans) and 4 other tissues.
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; IPR004101; Mur_ligase_C.
DR InterPro; IPR036615; Mur_ligase_C_dom_sf.
DR PANTHER; PTHR11136; PTHR11136; 1.
DR PANTHER; PTHR11136:SF5; PTHR11136:SF5; 1.
DR Pfam; PF02875; Mur_ligase_C; 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 3: Inferred from homology;
KW Alternative initiation; Alternative splicing; ATP-binding; Cytoplasm;
KW Ligase; Magnesium; Membrane; Metal-binding; Mitochondrion;
KW Mitochondrion inner membrane; Nucleotide-binding; One-carbon metabolism;
KW Reference proteome.
FT CHAIN 1..510
FT /note="Putative folylpolyglutamate synthase"
FT /id="PRO_0000168306"
FT BINDING 98..101
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 122
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 189
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 217
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 342
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 357
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT VAR_SEQ 1..26
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_041963"
FT VAR_SEQ 3..9
FT /note="LLPQTNR -> IISSIFAPTRGFHSRSTW (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_041964"
SQ SEQUENCE 510 AA; 56433 MW; 12A965157DFED84A CRC64;
MRLLPQTNRI LLPTTSSTAC GANQLRMSSE KAVPCYEESV RLLNGLQSNA ATIKKLRVQR
ENLQAINLPQ CRKYLESLNI SAEDLNALNI IHVSGTKGKG SACAFVESIL RSQGLRTGFY
SSPHLVHVRE RIQVDGQPVS EQMFAEEFFH VYDIIKREHS DNMPAYFKFL TLLAFRIFVK
LNVQVMILEV GIGGEYDCTN VVEKPKVCGV TTLDYDHMSI LGNKLSEIAW HKAGIFKESV
PAFYSPTTTE AEEVLIARAI SKHVPLFQTP PVSAYQFARD ISPGIRGAHQ FSNVSMALQL
VRAWAEKCGF PLPGVPLSTD TSGFNVPLWM CDAIESCRWP GRSQIVSTDR NVTYLLDGAH
TPKSMEACSE WAAEEIVNLK KENVKKILLF QCTADRCPST LIKYLKPLGI SQIVSCPTQL
HSSIDKSADS ANLNASRDEQ AEKANQCVQA WKESLDQPES VTEDQMKVFD CISSAYKFIE
SQAASQEILV LVTGSLHLVG GVLNLAGKGK
