FOLC_CRIGR
ID FOLC_CRIGR Reviewed; 587 AA.
AC Q924L9; Q64394; Q91XR4;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 96.
DE RecName: Full=Folylpolyglutamate synthase, mitochondrial;
DE EC=6.3.2.17;
DE AltName: Full=Folylpoly-gamma-glutamate synthetase;
DE Short=FPGS;
DE AltName: Full=Tetrahydrofolate synthase;
DE AltName: Full=Tetrahydrofolylpolyglutamate synthase;
DE Flags: Precursor;
GN Name=FPGS;
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS SER-173 AND GLU-536.
RC TISSUE=Kidney, and Lung;
RA Titus S.A. Jr., Fergeson J., Moran R.G.;
RT "Mutations causative of GAT class of somatic cell auxotrophs.";
RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-70 (ISOFORM 1), AND ALTERNATIVE INITIATION.
RC TISSUE=Ovary;
RX PubMed=7721888; DOI=10.1074/jbc.270.16.9579;
RA Freemantle S.J., Taylor S.M., Krystal G., Moran R.G.;
RT "Upstream organization of and multiple transcripts from the human
RT folylpoly-gamma-glutamate synthetase gene.";
RL J. Biol. Chem. 270:9579-9584(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: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 -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:Q05932}. Mitochondrion matrix
CC {ECO:0000250|UniProtKB:Q05932}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000250|UniProtKB:Q05932}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=1; Synonyms=Mitochondrial;
CC IsoId=Q924L9-1; Sequence=Displayed;
CC Name=2; Synonyms=Cytoplasmic;
CC IsoId=Q924L9-2; Sequence=VSP_041958;
CC -!- SIMILARITY: Belongs to the folylpolyglutamate synthase family.
CC {ECO:0000305}.
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DR EMBL; AF283646; AAK69545.1; -; mRNA.
DR EMBL; AF283647; AAK69546.1; -; mRNA.
DR EMBL; U14938; AAA85814.1; -; mRNA.
DR RefSeq; NP_001230938.1; NM_001244009.2. [Q924L9-1]
DR AlphaFoldDB; Q924L9; -.
DR SMR; Q924L9; -.
DR STRING; 10029.NP_001230938.1; -.
DR GeneID; 100689022; -.
DR KEGG; cge:100689022; -.
DR CTD; 2356; -.
DR eggNOG; KOG2525; Eukaryota.
DR OrthoDB; 840266at2759; -.
DR BRENDA; 6.3.2.17; 1309.
DR UniPathway; UPA00850; -.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
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; IEA:UniProtKB-EC.
DR GO; GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-KW.
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 2: Evidence at transcript level;
KW Alternative initiation; ATP-binding; Cytoplasm; Ligase; Magnesium;
KW Membrane; Metal-binding; Mitochondrion; Mitochondrion inner membrane;
KW Nucleotide-binding; One-carbon metabolism; Phosphoprotein; Transit peptide.
FT TRANSIT 1..42
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT CHAIN 43..587
FT /note="Folylpolyglutamate synthase, mitochondrial"
FT /id="PRO_5000058419"
FT REGION 484..508
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 106..109
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 130
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 200
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 228
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 363
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 377
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT MOD_RES 539
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q05932"
FT VAR_SEQ 1..42
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_041958"
FT VARIANT 173
FT /note="A -> S"
FT /evidence="ECO:0000269|Ref.1"
FT VARIANT 536
FT /note="Q -> E"
FT /evidence="ECO:0000269|Ref.1"
SQ SEQUENCE 587 AA; 65093 MW; 5DADD47B866FCD5F CRC64;
MSWARTHLRS ALSLAAVSAR GATTEGAARR WLSAWPAPQE PGMEYQDAVR MLNTLQTNAS
YLEQVKRQRS DPQAQLEAME VYLARSGLQV EDLNQLNIIH VTGTKGKGST CAFTERILRS
YGLKTGFFSS PHLVQVRERI RINGKPISPE LFTKHFWRLY HQLEEFKDDS HVAMPAYFRF
LTLMAFHVFL QEKVDLAVVE VGIGGAYDCT NIIRKPVVCG VSSLGMDHTS LLGDTVEKIA
WQKGGIFKPG VPAFTVLQPE GPLAVLRDRA QQTSCPLYLC PPLEALEDGG LPLTLGLEGE
HQRSNAALAL QLAHCWLEQQ DHQDIRELKV SRPSMRWQLP LAPVFHPTSH MRHGLRDTEW
PGRTQVLRRG PLTWYLDGAH TTSSVQACVR WYCQSLQRSK HPSGGPEVYV LLFNSTGDRD
SAALLKLLQP CQFDYAVFCP NLTEVSSTEN ADQQNFTVTL DQVLLRCLQH QQHWSCLSEK
QASPDFLSSP SPEPGRPGSL QPALRPPHST GTNSLVFSCI SHALQWISQG RDPIFQAPSP
PRSLLSHPTA SSGASILREA GAIHVLVTGS LHLVGGVLKL LEPSLSQ
