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Q05932 (FOLC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Folylpolyglutamate synthase, mitochondrial

EC=6.3.2.17
Alternative name(s):
Folylpoly-gamma-glutamate synthetase
Short name=FPGS
Tetrahydrofolylpolyglutamate synthase
Short name=Tetrahydrofolate synthase
Gene names
Name:FPGS
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length587 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes conversion of folates to polyglutamate derivatives allowing concentration of folate compounds in the cell and the intracellular retention of these cofactors, which are important substrates for most of the folate-dependent enzymes that are involved in one-carbon transfer reactions involved in purine, pyrimidine and amino acid synthesis. Unsubstitued reduced folates are the preferred substrates. Metabolizes methotrexate (MTX) to polyglutamates. Ref.4 Ref.8 Ref.9 Ref.11

Catalytic activity

ATP + tetrahydropteroyl-(gamma-Glu)(n) + L-glutamate = ADP + phosphate + tetrahydropteroyl-(gamma-Glu)(n+1). Ref.4 Ref.6 Ref.8 Ref.10 Ref.13 Ref.14

Cofactor

A monovalent cation. K+ is most effective, followed by NH4+ and Rb+. Na+, Li+ and Cs+ are ineffective. Ref.4

Enzyme regulation

Activated by 10 mM sodium bicarbonate. Ref.4

Pathway

Cofactor biosynthesis; tetrahydrofolylpolyglutamate biosynthesis.

Subunit structure

Monomer.

Subcellular location

Isoform 1: Mitochondrion inner membrane. Mitochondrion matrix Ref.4 Ref.10 Ref.12.

Isoform 2: Cytoplasm Ref.4 Ref.10 Ref.12.

Sequence similarities

Belongs to the folylpolyglutamate synthase family.

Biophysicochemical properties

Kinetic parameters:

KM=201 µM for L-glutamate (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate) Ref.4 Ref.13

KM=200 µM for MgATP (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)

KM=59 µM for pteroylglutamic acid (PteGlu) (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)

KM=16 µM for PteGlu2 (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)

KM=20 µM for PteGlu3 (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)

KM=12 µM for PteGlu4 (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)

KM=64 µM for PteGlu5 (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)

KM=0.81 µM for H2PteGlu (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)

KM=47 µM for H2PteGlu2 (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)

KM=1.6 µM for (6ambo)-tetrahydropteroylpoly-gamma-glutamate (H4PteGlu) (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)

KM=4.4 µM for (6S)-H4PteGlu (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)

KM=3.3 µM for (6S)-H4PteGlu2 (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)

KM=1.4 µM for (6S)-H4PteGlu3 (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)

KM=1.6 µM for (6S)-H4PteGlu4 (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)

KM=1.4 µM for (6S)-H4PteGlu5 (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)

KM=3.7 µM for (6R)-10-formyl-H4PteGlu (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)

KM=2.7 µM for (6R)-10-formyl-H4PteGlu2 (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)

KM=105 µM for (6S)-5-formyl-H4PteGlu (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)

KM=13 µM for (6S)-5-formyl-H4PteGlu2 (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)

KM=48 µM for (6S)-5-methyl-H4PteGlu (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)

KM=4.4 µM for aminopterin (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)

KM=55.5 µM for methotrexate (isoform 2, Ref.13, at 37 degrees Celsius in the presence of 10 mM ATP and pH 8.5)

KM=52.6 µM for methotrexate (isoform 1, Ref.13, at 37 degrees Celsius in the presence of 10 mM ATP and pH 8.5)

KM=71 µM for methotrexate (Glu-1) (isoform 2, Ref.4, at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)

KM=50 µM for methotrexate (Glu-2) (isoform 2, Ref.4, at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)

KM=148 µM for methotrexate (Glu-3) (isoform 2, Ref.4, at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)

KM=5.3 µM for 5-deazaacyclotetrahydrofolate (isoform 2, at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)

KM=2.8 µM for 2-methyl-5,8-dideazaisofolate (isoform 2, at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate)

KM=1702 µM for glutamic acid (isoform 2, Ref.13, at 37 degrees Celsius in the presence of 10 mM ATP and pH 8.5)

KM=2068 µM for glutamic acid (isoform 1, Ref.13, at 37 degrees Celsius in the presence of 10 mM ATP and pH 8.5)

Vmax=0.34 µmol/h/mg enzyme with methotrexate as substrate (isoform 2, Ref.13, at 37 degrees Celsius in the presence of 10 mM ATP and pH 8.5)

Vmax=0.05 µmol/h/mg enzyme with methotrexate as substrate (isoform 1, Ref.13, at 37 degrees Celsius in the presence of 10 mM ATP and pH 8.5)

Vmax=1.26 µmol/h/mg enzyme with glutamic acid as substrate (isoform 2, Ref.13, at 37 degrees Celsius in the presence of 10 mM ATP and pH 8.5)

Vmax=0.25 µmol/h/mg enzyme with glutamic acid as substrate (isoform 1, Ref.13, at 37 degrees Celsius in the presence of 10 mM ATP and pH 8.5)

pH dependence:

Optimum pH is 9.6 (isoform 2)

Sequence caution

The sequence AAA35852.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processOne-carbon metabolism
   Cellular componentCytoplasm
Membrane
Mitochondrion
Mitochondrion inner membrane
   Coding sequence diversityAlternative initiation
Alternative splicing
Polymorphism
   DomainTransit peptide
   LigandATP-binding
Nucleotide-binding
   Molecular functionLigase
   PTMAcetylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbrain development

Inferred from electronic annotation. Source: Ensembl

folic acid metabolic process

Traceable author statement. Source: Reactome

liver development

Inferred from electronic annotation. Source: Ensembl

nucleobase-containing compound metabolic process

Traceable author statement Ref.5. Source: ProtInc

one-carbon metabolic process

Inferred from electronic annotation. Source: UniProtKB-KW

organ regeneration

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

vitamin metabolic process

Traceable author statement. Source: Reactome

water-soluble vitamin metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasm

Traceable author statement Ref.6. Source: ProtInc

cytosol

Traceable author statement. Source: Reactome

mitochondrial inner membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrial matrix

Traceable author statement. Source: Reactome

mitochondrion

Traceable author statement Ref.5. Source: ProtInc

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

tetrahydrofolylpolyglutamate synthase activity

Traceable author statement Ref.5. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing and alternative initiation. [Align] [Select]
Isoform 1 (identifier: Q05932-1)

Also known as: Mitochondrial;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q05932-2)

Also known as: Cytoplasmic;

The sequence of this isoform differs from the canonical sequence as follows:
     1-42: Missing.
Note: Produced by alternative initiation at Met-43 of isoform 1.
Isoform 3 (identifier: Q05932-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-42: Missing.
     43-50: Missing.
Note: Produced by alternative splicing of isoform 1.
Isoform 4 (identifier: Q05932-4)

The sequence of this isoform differs from the canonical sequence as follows:
     168-193: Missing.
Note: Produced by alternative splicing of isoform 1.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 4242Mitochondrion
Chain43 – 587545Folylpolyglutamate synthase, mitochondrial
PRO_0000010097

Regions

Nucleotide binding103 – 1097ATP Potential

Amino acid modifications

Modified residue431N-acetylmethionine Ref.15

Natural variations

Alternative sequence1 – 4242Missing in isoform 2 and isoform 3.
VSP_018733
Alternative sequence43 – 508Missing in isoform 3.
VSP_041959
Alternative sequence168 – 19326Missing in isoform 4.
VSP_041960
Natural variant131F → L. Ref.13
Corresponds to variant rs11554717 [ dbSNP | Ensembl ].
VAR_066016
Natural variant221I → V. Ref.1 Ref.3 Ref.5
Corresponds to variant rs10760502 [ dbSNP | Ensembl ].
VAR_059305
Natural variant4371V → D.
Corresponds to variant rs12686275 [ dbSNP | Ensembl ].
VAR_043929
Natural variant4661R → C Expression reduced by 1.86-fold and Vmax with methotrexate as substrate reduced significantly. The intrinsic clearance of methotrexate is significantly reduced. Km of glutamic acid is increased 3.5-fold and apparent Vmax of it is reduced 3.4-fold. Reaction velocity at 100 nmol/L of pemetrexed is significantly reduced and folic acid dose-response curve is shifted to the right which corresponds to 4.32-fold increase in the EC(50) for folic acid. IC(50) of methotrexate is 1.84-fold higher and accumulation of a lower ratio of long-chain methotrexate polyglutamates to short-chain polyglutamates is detected. All results are for isoform 2 variant in comparison to the wild-type of it. Ref.13
Corresponds to variant rs35789560 [ dbSNP | Ensembl ].
VAR_066017
Natural variant4891A → V. Ref.3 Ref.13
Corresponds to variant rs17855900 [ dbSNP | Ensembl ].
VAR_043930
Natural variant4991S → F Expression reduced by 2.11-fold and Vmax with methotrexate as substrate reduced significantly. The intrinsic clearance of methotrexate is significantly reduced. Apparent Vmax for glutamic acid is reduced 5-fold. Reaction velocity at 100 nmol/L of pemetrexed is significantly reduced and folic acid dose-response curve is shifted to the right which corresponds to 4.28-fold increase in the EC(50) for folic acid. IC(50) of methotrexate is 1.64-fold higher and accumulation of a lower ratio of long-chain methotrexate polyglutamates to short-chain polyglutamates is detected. All results are for isoform 2 variant in comparison to the wild-type of it. Ref.13
Corresponds to variant rs200314440 [ dbSNP | Ensembl ].
VAR_066018
Natural variant5281S → T.
Corresponds to variant rs34354111 [ dbSNP | Ensembl ].
VAR_043931

Experimental info

Sequence conflict1011V → A in BAG51826. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Mitochondrial) [UniParc].

Last modified October 1, 1996. Version 3.
Checksum: 5AF81409F5F77E5C

FASTA58764,609
        10         20         30         40         50         60 
MSRARSHLRA ALFLAAASAR GITTQVAARR GLSAWPVPQE PSMEYQDAVR MLNTLQTNAG 

        70         80         90        100        110        120 
YLEQVKRQRG DPQTQLEAME LYLARSGLQV EDLDRLNIIH VTGTKGKGST CAFTECILRS 

       130        140        150        160        170        180 
YGLKTGFFSS PHLVQVRERI RINGQPISPE LFTKYFWRLY HRLEETKDGS CVSMPPYFRF 

       190        200        210        220        230        240 
LTLMAFHVFL QEKVDLAVVE VGIGGAYDCT NIIRKPVVCG VSSLGIDHTS LLGDTVEKIA 

       250        260        270        280        290        300 
WQKGGIFKQG VPAFTVLQPE GPLAVLRDRA QQISCPLYLC PMLEALEEGG PPLTLGLEGE 

       310        320        330        340        350        360 
HQRSNAALAL QLAHCWLQRQ DRHGAGEPKA SRPGLLWQLP LAPVFQPTSH MRLGLRNTEW 

       370        380        390        400        410        420 
PGRTQVLRRG PLTWYLDGAH TASSAQACVR WFRQALQGRE RPSGGPEVRV LLFNATGDRD 

       430        440        450        460        470        480 
PAALLKLLQP CQFDYAVFCP NLTEVSSTGN ADQQNFTVTL DQVLLRCLEH QQHWNHLDEE 

       490        500        510        520        530        540 
QASPDLWSAP SPEPGGSASL LLAPHPPHTC SASSLVFSCI SHALQWISQG RDPIFQPPSP 

       550        560        570        580 
PKGLLTHPVA HSGASILREA AAIHVLVTGS LHLVGGVLKL LEPALSQ 

« Hide

Isoform 2 (Cytoplasmic) [UniParc].

Checksum: 59650383900A309E
Show »

FASTA54560,167
Isoform 3 [UniParc].

Checksum: 4FA022E884342D11
Show »

FASTA53759,174
Isoform 4 [UniParc].

Checksum: 243138601850E090
Show »

FASTA56161,562

References

« Hide 'large scale' references
[1]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4), VARIANT VAL-22.
[2]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS VAL-22 AND VAL-489.
Tissue: Lung.
[4]"Purification and properties of human cytosolic folylpoly-gamma-glutamate synthetase and organization, localization, and differential splicing of its gene."
Chen L., Qi H., Korenberg J., Garrow T.A., Choi Y.J., Shane B.
J. Biol. Chem. 271:13077-13087(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-353, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE SPECIFICITY, SUBCELLULAR LOCATION, ALTERNATIVE SPLICING.
Tissue: Fibroblast.
[5]"Upstream organization of and multiple transcripts from the human folylpoly-gamma-glutamate synthetase gene."
Freemantle S.J., Taylor S.M., Krystal G., Moran R.G.
J. Biol. Chem. 270:9579-9584(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-107, ALTERNATIVE INITIATION, VARIANT VAL-22.
Tissue: Placenta.
[6]"Expression cloning of a human cDNA encoding folylpoly(gamma-glutamate) synthetase and determination of its primary structure."
Garrow T.A., Admon A., Shane B.
Proc. Natl. Acad. Sci. U.S.A. 89:9151-9155(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 20-587 (ISOFORM 1), CATALYTIC ACTIVITY.
Tissue: Lymphocyte.
[7]"Structural organization of the human folypoly-gamma-glutamate synthetase gene: evidence for a single genomic locus."
Taylor S.M., Freemantle S.J., Moran R.G.
Cancer Res. 55:6030-6034(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 102-587.
Tissue: Placenta.
[8]"Regulation of folate and one-carbon metabolism in mammalian cells. I. Folate metabolism in Chinese hamster ovary cells expressing Escherichia coli or human folylpoly-gamma-glutamate synthetase activity."
Osborne C.B., Lowe K.E., Shane B.
J. Biol. Chem. 268:21657-21664(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY.
[9]"Regulation of folate and one-carbon metabolism in mammalian cells. II. Effect of folylpoly-gamma-glutamate synthetase substrate specificity and level on folate metabolism and folylpoly-gamma-glutamate specificity of metabolic cycles of one-carbon metabolism."
Lowe K.E., Osborne C.B., Lin B.F., Kim J.S., Hsu J.C., Shane B.
J. Biol. Chem. 268:21665-21673(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Regulation of folate and one-carbon metabolism in mammalian cells. III. Role of mitochondrial folylpoly-gamma-glutamate synthetase."
Lin B.F., Huang R.F., Shane B.
J. Biol. Chem. 268:21674-21679(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, SUBCELLULAR LOCATION.
[11]"Regulation of folate and one-carbon metabolism in mammalian cells. IV. Role of folylpoly-gamma-glutamate synthetase in methotrexate metabolism and cytotoxicity."
Kim J.S., Lowe K.E., Shane B.
J. Biol. Chem. 268:21680-21685(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"Submitochondrial localization of the mitochondrial isoform of folylpolyglutamate synthetase in CCRF-CEM human T-lymphoblastic leukemia cells."
Nair J.R., McGuire J.J.
Biochim. Biophys. Acta 1746:38-44(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[13]"Identification and characterization of genetic variation in the folylpolyglutamate synthase gene."
Leil T.A., Endo C., Adjei A.A., Dy G.K., Salavaggione O.E., Reid J.R., Ames M.M., Adjei A.A.
Cancer Res. 67:8772-8782(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, VARIANTS LEU-13; CYS-466; VAL-489 AND PHE-499.
[14]"Concentration-dependent processivity of multiple glutamate ligations catalyzed by folylpoly-gamma-glutamate synthetase."
Tomsho J.W., Moran R.G., Coward J.K.
Biochemistry 47:9040-9050(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, REACTION MECHANISM.
[15]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-43, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK056920 mRNA. Translation: BAG51826.1.
AK295309 mRNA. Translation: BAH12029.1.
AL162586 Genomic DNA. Translation: CAI39770.1.
AL162586 Genomic DNA. Translation: CAI39773.1.
BC064393 mRNA. Translation: AAH64393.1.
AH006037 Genomic DNA. Translation: AAC13871.1.
M98045 mRNA. Translation: AAA35852.1. Different initiation.
U14939 Genomic DNA. Translation: AAA85815.1.
AH003340 Genomic DNA. Translation: AAA87568.1.
PIRA46281.
RefSeqNP_001018088.1. NM_001018078.2.
NP_001275732.1. NM_001288803.1.
NP_004948.4. NM_004957.5.
UniGeneHs.335084.

3D structure databases

ProteinModelPortalQ05932.
SMRQ05932. Positions 41-582.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108639. 1 interaction.
STRING9606.ENSP00000362344.

Chemistry

BindingDBQ05932.
ChEMBLCHEMBL3171.
DrugBankDB00142. L-Glutamic Acid.

PTM databases

PhosphoSiteQ05932.

Polymorphism databases

DMDM1706884.

Proteomic databases

PaxDbQ05932.
PRIDEQ05932.

Protocols and materials databases

DNASU2356.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000373225; ENSP00000362322; ENSG00000136877. [Q05932-3]
ENST00000373247; ENSP00000362344; ENSG00000136877. [Q05932-1]
ENST00000393706; ENSP00000377309; ENSG00000136877. [Q05932-4]
GeneID2356.
KEGGhsa:2356.
UCSCuc004bsg.1. human. [Q05932-1]
uc011mal.1. human. [Q05932-4]

Organism-specific databases

CTD2356.
GeneCardsGC09P130556.
HGNCHGNC:3824. FPGS.
HPAHPA050488.
MIM136510. gene+phenotype.
neXtProtNX_Q05932.
PharmGKBPA167.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0285.
HOGENOMHOG000181278.
HOVERGENHBG003086.
InParanoidQ05932.
KOK01930.
OMAIPEMVEY.
OrthoDBEOG7T7GTN.
PhylomeDBQ05932.
TreeFamTF313956.

Enzyme and pathway databases

BioCycMetaCyc:HS06237-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.
UniPathwayUPA00850.

Gene expression databases

ArrayExpressQ05932.
BgeeQ05932.
CleanExHS_FPGS.
GenevestigatorQ05932.

Family and domain databases

Gene3D3.40.1190.10. 1 hit.
3.90.190.20. 3 hits.
InterProIPR001645. Folylpolyglutamate_synth.
IPR018109. Folylpolyglutamate_synth_CS.
IPR023600. Folylpolyglutamate_synth_euk.
IPR004101. Mur_ligase_C.
IPR013221. Mur_ligase_cen.
[Graphical view]
PANTHERPTHR11136. PTHR11136. 1 hit.
PIRSFPIRSF038895. FPGS. 1 hit.
SUPFAMSSF53244. SSF53244. 1 hit.
SSF53623. SSF53623. 1 hit.
TIGRFAMsTIGR01499. folC. 1 hit.
PROSITEPS01011. FOLYLPOLYGLU_SYNT_1. 1 hit.
PS01012. FOLYLPOLYGLU_SYNT_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiFPGS.
GenomeRNAi2356.
NextBio9555.
PROQ05932.
SOURCESearch...

Entry information

Entry nameFOLC_HUMAN
AccessionPrimary (citable) accession number: Q05932
Secondary accession number(s): B3KPW4 expand/collapse secondary AC list , B7Z2Z3, F5H0K6, Q5JU19, Q5JU22, Q6P2P6
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: October 1, 1996
Last modified: April 16, 2014
This is version 142 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM