FOLC_MOUSE
ID FOLC_MOUSE Reviewed; 587 AA.
AC P48760; A2AK69; Q3U0B4; Q99K38;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 183.
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=Tetrahydrofolylpolyglutamate synthase;
DE Short=Tetrahydrofolate synthase;
DE Flags: Precursor;
GN Name=Fpgs;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND CATALYTIC ACTIVITY.
RX PubMed=7592937; DOI=10.1074/jbc.270.45.26918;
RA Roy K., Mitsugi K., Sirlin S., Shane B., Sirotnak F.M.;
RT "Different antifolate-resistant L1210 cell variants with either increased
RT or decreased folylpolyglutamate synthetase gene expression at the level of
RT mRNA transcription.";
RL J. Biol. Chem. 270:26918-26922(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND ALTERNATIVE INITIATION.
RC STRAIN=DBA/2J;
RX PubMed=8605241; DOI=10.1016/0167-4781(95)00193-x;
RA Spinella M.J., Brigle K.E., Goldman I.D.;
RT "Molecular cloning of murine folylpoly-gamma-glutamate synthetase.";
RL Biochim. Biophys. Acta 1305:11-14(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING, AND
RP ALTERNATIVE INITIATION.
RX PubMed=8798611; DOI=10.1074/jbc.271.39.23820;
RA Roy K., Mitsugi K., Sirotnak F.M.;
RT "Organization and alternate splicing of the murine folylpolyglutamate
RT synthetase gene. Different splice variants in L1210 cells encode
RT mitochondrial or cytosolic forms of the enzyme.";
RL J. Biol. Chem. 271:23820-23827(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE PROMOTER USAGE,
RP ALTERNATIVE SPLICING, ALTERNATIVE INITIATION, AND TISSUE SPECIFICITY.
RX PubMed=9038166; DOI=10.1074/jbc.272.9.5587;
RA Roy K., Mitsugi K., Sirotnak F.M.;
RT "Additional organizational features of the murine folylpolyglutamate
RT synthetase gene. Two remotely situated exons encoding an alternate 5' end
RT and proximal open rea ding frame under the control of a second promoter.";
RL J. Biol. Chem. 272:5587-5593(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=NOD; TISSUE=Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4-587 (ISOFORM 1).
RC TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND SUBSTRATE SPECIFICITY.
RX PubMed=6548641; DOI=10.1021/bi00315a011;
RA Moran R.G., Colman P.D.;
RT "Mammalian folyl polyglutamate synthetase: partial purification and
RT properties of the mouse liver enzyme.";
RL Biochemistry 23:4580-4589(1984).
RN [10]
RP ENZYME KINETICS, SUBSTRATE SPECIFICITY, AND TISSUE SPECIFICITY.
RX PubMed=10626793;
RA Turner F.B., Andreassi J.L., Ferguson J., Titus S., Tse A., Taylor S.M.,
RA Moran R.G.;
RT "Tissue-specific expression of functional isoforms of mouse folypoly-gamma-
RT glutamae synthetase: a basis for targeting folate antimetabolites.";
RL Cancer Res. 59:6074-6079(1999).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND ENZYME KINETICS.
RX PubMed=11772020; DOI=10.1021/bi015644d;
RA Andreassi J.L. II, Moran R.G.;
RT "Mouse folylpoly-gamma-glutamate synthetase isoforms respond differently to
RT feedback inhibition by folylpolyglutamate cofactors.";
RL Biochemistry 41:226-235(2002).
RN [12]
RP ALTERNATIVE PROMOTER USAGE, AND TISSUE SPECIFICITY.
RX PubMed=17998333; DOI=10.1128/mcb.01088-07;
RA Racanelli A.C., Turner F.B., Xie L.Y., Taylor S.M., Moran R.G.;
RT "A mouse gene that coordinates epigenetic controls and transcriptional
RT interference to achieve tissue-specific expression.";
RL Mol. Cell. Biol. 28:836-848(2008).
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. Dihydrofolate, tetrahydrofolate, 5,10-
CC methylenetetrahydrofolate, 10-formyltetrahydrofolate and 5-
CC formyltetrahydrofolate are the best substrates. Folic acid and 5-
CC methyltetrahydrofolate can also act as substrates.
CC {ECO:0000269|PubMed:11772020, ECO:0000269|PubMed:6548641}.
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:11772020, ECO:0000269|PubMed:6548641,
CC ECO:0000269|PubMed:7592937};
CC -!- COFACTOR:
CC Name=a monovalent cation; Xref=ChEBI:CHEBI:60242;
CC Evidence={ECO:0000250};
CC Note=A monovalent cation. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Inhibited by ammonium sulfate. Inhibited by
CC pentaglutamate derivative of DDATHF, but isoform 2 is inhibited to a
CC greater extent at lower concentrations of the compound that is isoform
CC 5. Isoform 5 is virtually unaffected by H(4)PteGlu(5) and 5,10-CH(2)-
CC H(4)PteGlu(5) at concentrations that substantially inhibits the
CC activity of isoform 2. Isoform 2 and 5 are equally sensitive to
CC polyglutamates of 10-CHO-H(4)-PteGlu. {ECO:0000269|PubMed:11772020,
CC ECO:0000269|PubMed:6548641}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=17.7 uM for aminopterin (isoform 5 at 34 degrees Celsius and pH
CC 8.9) {ECO:0000269|PubMed:11772020, ECO:0000269|PubMed:6548641};
CC KM=15.4 uM for aminopterin (isoform 2 at 34 degrees Celsius and pH
CC 8.9) {ECO:0000269|PubMed:11772020, ECO:0000269|PubMed:6548641};
CC KM=7.6 uM for (6R)-DDATHF (isoform 5 at 34 degrees Celsius and pH
CC 8.9) {ECO:0000269|PubMed:11772020, ECO:0000269|PubMed:6548641};
CC KM=1.2 uM for (6R)-DDATHF (isoform 2 at 34 degrees Celsius and pH
CC 8.9) {ECO:0000269|PubMed:11772020, ECO:0000269|PubMed:6548641};
CC KM=6.3 uM for (6S)-H(4)PteGlu (isoform 5 at 34 degrees Celsius and pH
CC 8.9) {ECO:0000269|PubMed:11772020, ECO:0000269|PubMed:6548641};
CC KM=1.4 uM for (6S)-H(4)PteGlu (isoform 2 at 34 degrees Celsius and pH
CC 8.9) {ECO:0000269|PubMed:11772020, ECO:0000269|PubMed:6548641};
CC KM=2.9 uM for (6R)-10-CHO-H(4)PteGlu (isoform 5 at 34 degrees Celsius
CC and pH 8.9) {ECO:0000269|PubMed:11772020,
CC ECO:0000269|PubMed:6548641};
CC KM=2.0 uM for (6R)-10-CHO-H(4)PteGlu (isoform 2 at 34 degrees Celsius
CC and pH 8.9) {ECO:0000269|PubMed:11772020,
CC ECO:0000269|PubMed:6548641};
CC KM=64 uM for (6S)-5-CH(3)-H(4)PteGlu (isoform 5 at 34 degrees Celsius
CC and pH 8.9) {ECO:0000269|PubMed:11772020,
CC ECO:0000269|PubMed:6548641};
CC KM=54 uM for (6S)-5-CH(3)-H(4)PteGlu (isoform 2 at 34 degrees Celsius
CC and pH 8.9) {ECO:0000269|PubMed:11772020,
CC ECO:0000269|PubMed:6548641};
CC KM=122 uM for (6S)-5-CHO-H(4)PteGlu (isoform 5 at 34 degrees Celsius
CC and pH 8.9) {ECO:0000269|PubMed:11772020,
CC ECO:0000269|PubMed:6548641};
CC KM=75 uM for (6S)-5-CHO-H(4)PteGlu (isoform 2 at 34 degrees Celsius
CC and pH 8.9) {ECO:0000269|PubMed:11772020,
CC ECO:0000269|PubMed:6548641};
CC pH dependence:
CC Optimum pH is 8.2-9.5 using 500 uM folic acid (PteGlu) and 25 uM dl-
CC 5-formyltetrahydrofolate (dl-5-CHO-H(4)PteGlu) as substrates.
CC {ECO:0000269|PubMed:11772020, ECO:0000269|PubMed:6548641};
CC Temperature dependence:
CC Optimum temperature is 37 degrees Celsius. Activity completely lost
CC within a few hours at 4 degrees Celsius in the absence of ATP and
CC glycerol. {ECO:0000269|PubMed:11772020, ECO:0000269|PubMed:6548641};
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 promoter usage, Alternative splicing, Alternative initiation; Named isoforms=5;
CC Name=1; Synonyms=Mitochondrial;
CC IsoId=P48760-1; Sequence=Displayed;
CC Name=2; Synonyms=Cytoplasmic;
CC IsoId=P48760-2; Sequence=VSP_018734;
CC Name=3;
CC IsoId=P48760-3; Sequence=VSP_041961;
CC Name=4;
CC IsoId=P48760-4; Sequence=VSP_041962;
CC Name=5;
CC IsoId=P48760-5; Sequence=VSP_041967;
CC -!- TISSUE SPECIFICITY: With non-specific probe, highest content in kidney
CC and liver and lowest in spleen, lung and small intestine, and readily
CC detectable in all of the tumors except hepatoma. Isoform 1 and isoform
CC 2 expressed in leukemic cells and isoform 4 and isoform 5 in liver
CC cells. Isoform 1 and isoform 2 exclusively expressed in hepatoma and
CC Lewis lung carcinoma. Isoform 1 and isoform 2 also expressed in bone
CC marrow, small intestine and spleen. Kidney expresses isoform 1, isoform
CC 2, isoform 4 and isoform 5. {ECO:0000269|PubMed:10626793,
CC ECO:0000269|PubMed:17998333, ECO:0000269|PubMed:9038166}.
CC -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative initiation at Met-
CC 43 of isoform 1. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: Produced by alternative splicing of isoform
CC 1. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 4]: Produced by alternative promoter usage.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 5]: Produced by alternative initiation at Met-
CC 24 of isoform 4. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the folylpolyglutamate synthase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH05484.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U33557; AAC52812.1; -; mRNA.
DR EMBL; U32197; AAC52426.1; -; mRNA.
DR EMBL; AK157040; BAE33941.1; -; mRNA.
DR EMBL; AL772271; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466542; EDL08563.1; -; Genomic_DNA.
DR EMBL; BC005484; AAH05484.1; ALT_INIT; mRNA.
DR CCDS; CCDS15926.1; -. [P48760-1]
DR PIR; I49357; I49357.
DR PIR; S65755; S65755.
DR RefSeq; NP_034366.2; NM_010236.2. [P48760-1]
DR AlphaFoldDB; P48760; -.
DR SMR; P48760; -.
DR BioGRID; 199731; 1.
DR STRING; 10090.ENSMUSP00000028148; -.
DR BindingDB; P48760; -.
DR ChEMBL; CHEMBL2890; -.
DR DrugCentral; P48760; -.
DR iPTMnet; P48760; -.
DR PhosphoSitePlus; P48760; -.
DR EPD; P48760; -.
DR MaxQB; P48760; -.
DR PaxDb; P48760; -.
DR PeptideAtlas; P48760; -.
DR PRIDE; P48760; -.
DR ProteomicsDB; 267506; -. [P48760-1]
DR ProteomicsDB; 267507; -. [P48760-2]
DR ProteomicsDB; 267508; -. [P48760-3]
DR ProteomicsDB; 267509; -. [P48760-4]
DR ProteomicsDB; 267510; -. [P48760-5]
DR Antibodypedia; 30819; 166 antibodies from 23 providers.
DR DNASU; 14287; -.
DR Ensembl; ENSMUST00000028148; ENSMUSP00000028148; ENSMUSG00000009566. [P48760-1]
DR GeneID; 14287; -.
DR KEGG; mmu:14287; -.
DR UCSC; uc008jgm.2; mouse. [P48760-1]
DR CTD; 2356; -.
DR MGI; MGI:95576; Fpgs.
DR VEuPathDB; HostDB:ENSMUSG00000009566; -.
DR eggNOG; KOG2525; Eukaryota.
DR GeneTree; ENSGT00390000016526; -.
DR HOGENOM; CLU_015869_0_2_1; -.
DR InParanoid; P48760; -.
DR OMA; FFFEVWD; -.
DR OrthoDB; 840266at2759; -.
DR PhylomeDB; P48760; -.
DR TreeFam; TF313956; -.
DR BRENDA; 6.3.2.17; 3474.
DR Reactome; R-MMU-196757; Metabolism of folate and pterines.
DR UniPathway; UPA00850; -.
DR BioGRID-ORCS; 14287; 19 hits in 75 CRISPR screens.
DR PRO; PR:P48760; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P48760; protein.
DR Bgee; ENSMUSG00000009566; Expressed in left lobe of liver and 205 other tissues.
DR ExpressionAtlas; P48760; baseline and differential.
DR Genevisible; P48760; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
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; HDA:MGI.
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; ISO:MGI.
DR GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0008283; P:cell population proliferation; ISO:MGI.
DR GO; GO:0009396; P:folic acid-containing compound biosynthetic process; IBA:GO_Central.
DR GO; GO:0006760; P:folic acid-containing compound metabolic process; ISO:MGI.
DR GO; GO:0006536; P:glutamate metabolic process; ISO:MGI.
DR GO; GO:0001889; P:liver development; IEA:Ensembl.
DR GO; GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0046901; P:tetrahydrofolylpolyglutamate biosynthetic process; ISO:MGI.
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 Alternative initiation; Alternative promoter usage; Alternative splicing;
KW ATP-binding; Cytoplasm; Ligase; Magnesium; Membrane; Metal-binding;
KW Mitochondrion; Mitochondrion inner membrane; Nucleotide-binding;
KW One-carbon metabolism; Phosphoprotein; Reference proteome; Transit peptide.
FT TRANSIT 1..42
FT /note="Mitochondrion"
FT CHAIN 43..587
FT /note="Folylpolyglutamate synthase, mitochondrial"
FT /id="PRO_0000010099"
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..46
FT /note="MSWARSRLCSTLSLAAVSARGATTEGAARRGMSAWPAPQEPGMEYQ -> MM
FT KSTRSLPMSWPVREKFWWEAAMEWKDPSGSAYEAKTASFQ (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_041962"
FT VAR_SEQ 1..46
FT /note="MSWARSRLCSTLSLAAVSARGATTEGAARRGMSAWPAPQEPGMEYQ -> ME
FT WKDPSGSAYEAKTASFQ (in isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_041967"
FT VAR_SEQ 1..42
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_018734"
FT VAR_SEQ 1..15
FT /note="MSWARSRLCSTLSLA -> MAVIRRCFSLVRENLETRI (in isoform
FT 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_041961"
FT CONFLICT 27
FT /note="A -> P (in Ref. 1; AAC52812, 3; no nucleotide entry
FT and 4; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 35
FT /note="W -> G (in Ref. 1; AAC52812, 3; no nucleotide entry
FT and 4; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 75..76
FT /note="QL -> HV (in Ref. 2; AAC52426)"
FT /evidence="ECO:0000305"
FT CONFLICT 129
FT /note="S -> R (in Ref. 1; AAC52812 and 3; no nucleotide
FT entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 138
FT /note="E -> D (in Ref. 1; AAC52812 and 3; no nucleotide
FT entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 464
FT /note="L -> M (in Ref. 5; BAE33941)"
FT /evidence="ECO:0000305"
FT CONFLICT 491
FT /note="G -> S (in Ref. 2; AAC52426)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 587 AA; 64955 MW; B93261CBA110CA41 CRC64;
MSWARSRLCS TLSLAAVSAR GATTEGAARR GMSAWPAPQE PGMEYQDAVR TLNTLQTNAS
YLEQVKRQRS DPQAQLEAME MYLARSGLQV EDLNRLNIIH VTGTKGKGST CAFTERILRN
YGLKTGFFSS PHMVQVRERI RINGKPISPE LFTKHFWCLY NQLEEFKDDS HVSMPSYFRF
LTLMAFHVFL QEKVDLAVVE VGIGGAFDCT NIIRKPVVCG VSSLGIDHTS LLGDTVEKIA
WQKGGIFKPG VPAFTVVQPE GPLAVLRDRA QQIGCPLYLC PPLEALEEVG LPLSLGLEGA
HQRSNAALAL QLAHCWLERQ DHQDIQELKV SRPSIRWQLP LAPVFRPTPH MRRGLRDTVW
PGRTQILQRG PLTWYLDGAH TTSSVQACVH WYRQSLERSK RTDGGSEVHI LLFNSTGDRD
SAALLKLLQP CQFDYAVFCP NVTEVSSIGN ADQQNFTVTL DQVLLRCLQH QQHWNGLAEK
QASSNLWSSC GPDPAGPGSL LLAPHPPQPT RTSSLVFSCI SHALLWISQG RDPIFQPQSL
PRNLLNHPTA NSGASILREA AAIHVLVTGS LHLVGGVLKL LDPSMSQ
