ID   FOLC_HUMAN              Reviewed;         587 AA.
AC   Q05932; Q5JU22; Q6P2P6;
DT   01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 3.
DT   07-JUL-2009, entry version 92.
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   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164053; DOI=10.1038/nature02465;
RA   Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA   Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA   Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA   Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA   Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA   Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA   Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA   Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA   Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA   Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA   Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA   Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA   Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA   Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA   Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA   Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA   Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA   Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA   McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA   Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA   Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA   Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA   Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA   Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA   Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA   Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA   Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA   Rogers J., Dunham I.;
RT   "DNA sequence and analysis of human chromosome 9.";
RL   Nature 429:369-374(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-489.
RC   TISSUE=Lung;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-353.
RA   Chen L., Qi H., Korenberg J., Shane B.;
RT   "Alternate splicing and transcription start sites of the human
RT   folylpolyglutamate synthetase gene.";
RL   Submitted (JUL-1995) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 20-587.
RC   TISSUE=Lymphocyte;
RX   MEDLINE=93028422; PubMed=1409616; DOI=10.1073/pnas.89.19.9151;
RA   Garrow T.A., Admon A., Shane B.;
RT   "Expression cloning of a human cDNA encoding folylpoly(gamma-
RT   glutamate) synthetase and determination of its primary structure.";
RL   Proc. Natl. Acad. Sci. U.S.A. 89:9151-9155(1992).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-107, AND ALTERNATIVE
RP   INITIATION.
RC   TISSUE=Placenta;
RX   MEDLINE=95238480; 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).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 102-587.
RC   TISSUE=Placenta;
RX   MEDLINE=96105015; PubMed=8521387;
RA   Taylor S.M., Freemantle S.J., Moran R.G.;
RT   "Structural organization of the human folypoly-gamma-glutamate
RT   synthetase gene: evidence for a single genomic locus.";
RL   Cancer Res. 55:6030-6034(1995).
RN   [7]
RP   CHARACTERIZATION.
RX   MEDLINE=87157665; PubMed=3828320; DOI=10.1021/bi00376a024;
RA   Cichowicz D.J., Shane B.;
RT   "Mammalian folylpoly-gamma-glutamate synthetase. 1. Purification and
RT   general properties of the hog liver enzyme.";
RL   Biochemistry 26:504-512(1987).
CC   -!- FUNCTION: Conversion of folates to polyglutamate derivatives. This
CC       allows tissues to concentrate folate at higher levels than in
CC       plasma.
CC   -!- CATALYTIC ACTIVITY: ATP + tetrahydropteroyl-(gamma-Glu)(n) + L-
CC       glutamate = ADP + phosphate + tetrahydropteroyl-(gamma-Glu)(n+1).
CC   -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolylpolyglutamate
CC       biosynthesis.
CC   -!- SUBUNIT: Monomer.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion. Cytoplasm.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative initiation; Named isoforms=2;
CC       Name=Mitochondrial;
CC         IsoId=Q05932-1; Sequence=Displayed;
CC       Name=Cytoplasmic;
CC         IsoId=Q05932-2; Sequence=VSP_018733;
CC   -!- SIMILARITY: Belongs to the folylpolyglutamate synthase family.
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DR   EMBL; AL162586; CAI39770.1; -; Genomic_DNA.
DR   EMBL; BC064393; AAH64393.1; -; mRNA.
DR   EMBL; U24253; AAC13871.1; -; Genomic_DNA.
DR   EMBL; U24252; AAC13871.1; JOINED; Genomic_DNA.
DR   EMBL; M98045; AAA35852.1; ALT_INIT; mRNA.
DR   EMBL; U14939; AAA85815.1; -; Genomic_DNA.
DR   EMBL; U40868; AAA87568.1; -; Genomic_DNA.
DR   EMBL; U40863; AAA87568.1; JOINED; Genomic_DNA.
DR   EMBL; U40864; AAA87568.1; JOINED; Genomic_DNA.
DR   EMBL; U40865; AAA87568.1; JOINED; Genomic_DNA.
DR   EMBL; U40866; AAA87568.1; JOINED; Genomic_DNA.
DR   EMBL; U40867; AAA87568.1; JOINED; Genomic_DNA.
DR   IPI; IPI00016745; -.
DR   IPI; IPI00759584; -.
DR   PIR; A46281; A46281.
DR   RefSeq; NP_001018088.1; -.
DR   RefSeq; NP_004948.4; -.
DR   UniGene; Hs.335084; -.
DR   HSSP; P15925; 1FGS.
DR   PhosphoSite; Q05932; -.
DR   PRIDE; Q05932; -.
DR   Ensembl; ENSG00000136877; Homo sapiens.
DR   GeneID; 2356; -.
DR   KEGG; hsa:2356; -.
DR   UCSC; uc004bsg.1; human.
DR   GeneCards; GC09P129604; -.
DR   H-InvDB; HIX0008410; -.
DR   HGNC; HGNC:3824; FPGS.
DR   MIM; 136510; gene+phenotype.
DR   PharmGKB; PA167; -.
DR   HOGENOM; Q05932; -.
DR   HOVERGEN; Q05932; -.
DR   OMA; Q05932; GIDHTFM.
DR   BRENDA; 6.3.2.17; 247.
DR   Reactome; REACT_11193; Metabolism of vitamins and cofactors.
DR   DrugBank; DB00142; L-Glutamic Acid.
DR   NextBio; 9555; -.
DR   Bgee; Q05932; -.
DR   CleanEx; HS_FPGS; -.
DR   GermOnline; ENSG00000136877; Homo sapiens.
DR   GO; GO:0005829; C:cytosol; TAS:ProtInc.
DR   GO; GO:0005739; C:mitochondrion; TAS:ProtInc.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004326; F:tetrahydrofolylpolyglutamate synthase activity; TAS:ProtInc.
DR   GO; GO:0009396; P:folic acid and derivative biosynthetic process; IEA:InterPro.
DR   GO; GO:0006139; P:nucleobase, nucleoside, nucleotide and nucl...; TAS:ProtInc.
DR   GO; GO:0006730; P:one-carbon compound metabolic process; IEA:UniProtKB-KW.
DR   InterPro; IPR018109; Folylpolyglutamate_synth_CS.
DR   InterPro; IPR001645; Fpolygl_synthtse.
DR   InterPro; IPR004101; Mur_ligase_C.
DR   InterPro; IPR013221; Mur_ligase_cen.
DR   Gene3D; G3DSA:3.90.190.20; Mur_ligase_C; 1.
DR   Gene3D; G3DSA:3.40.1190.10; Mur_ligase_cen; 1.
DR   PANTHER; PTHR11136; Fpolygl_synthtse; 1.
DR   Pfam; PF02875; Mur_ligase_C; 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; ATP-binding; Complete proteome; Cytoplasm;
KW   Ligase; Mitochondrion; Nucleotide-binding; One-carbon metabolism;
KW   Phosphoprotein; Polymorphism; Transit peptide.
FT   TRANSIT       1     42       Mitochondrion.
FT   CHAIN        43    587       Folylpolyglutamate synthase,
FT                                mitochondrial.
FT                                /FTId=PRO_0000010097.
FT   NP_BIND     103    109       ATP (Potential).
FT   MOD_RES      33     33       Phosphoserine (By similarity).
FT   VAR_SEQ       1     42       Missing (in isoform Cytoplasmic).
FT                                /FTId=VSP_018733.
FT   VARIANT     437    437       V -> D (in dbSNP:rs12686275).
FT                                /FTId=VAR_043929.
FT   VARIANT     489    489       A -> V (in dbSNP:rs17855900).
FT                                /FTId=VAR_043930.
FT   VARIANT     528    528       S -> T (in dbSNP:rs34354111).
FT                                /FTId=VAR_043931.
FT   CONFLICT     22     22       I -> V (in Ref. 2; AAH64393 and 5;
FT                                AAA85815).
SQ   SEQUENCE   587 AA;  64609 MW;  5AF81409F5F77E5C CRC64;
     MSRARSHLRA ALFLAAASAR GITTQVAARR GLSAWPVPQE PSMEYQDAVR MLNTLQTNAG
     YLEQVKRQRG DPQTQLEAME LYLARSGLQV EDLDRLNIIH VTGTKGKGST CAFTECILRS
     YGLKTGFFSS PHLVQVRERI RINGQPISPE LFTKYFWRLY HRLEETKDGS CVSMPPYFRF
     LTLMAFHVFL QEKVDLAVVE VGIGGAYDCT NIIRKPVVCG VSSLGIDHTS LLGDTVEKIA
     WQKGGIFKQG VPAFTVLQPE GPLAVLRDRA QQISCPLYLC PMLEALEEGG PPLTLGLEGE
     HQRSNAALAL QLAHCWLQRQ DRHGAGEPKA SRPGLLWQLP LAPVFQPTSH MRLGLRNTEW
     PGRTQVLRRG PLTWYLDGAH TASSAQACVR WFRQALQGRE RPSGGPEVRV LLFNATGDRD
     PAALLKLLQP CQFDYAVFCP NLTEVSSTGN ADQQNFTVTL DQVLLRCLEH QQHWNHLDEE
     QASPDLWSAP SPEPGGSASL LLAPHPPHTC SASSLVFSCI SHALQWISQG RDPIFQPPSP
     PKGLLTHPVA HSGASILREA AAIHVLVTGS LHLVGGVLKL LEPALSQ
//