Q05932 (FOLC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	587 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	One-carbon metabolism
Cellular component	Cytoplasm Membrane Mitochondrion Mitochondrion inner membrane
Coding sequence diversity	Alternative initiation Alternative splicing Polymorphism
Domain	Transit peptide
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	brain development Inferred from electronic annotation. Source: Compara folic acid metabolic process Traceable author statement. Source: Reactome liver development Inferred from electronic annotation. Source: Compara 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: Compara response to chemical stimulus Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Traceable author statement. Source: Reactome mitochondrial inner membrane Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrial matrix Traceable author statement. Source: Reactome
Molecular_function	ATP 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 42	42	Mitochondrion
	Chain	43 – 587	545	Folylpolyglutamate synthase, mitochondrial		PRO_0000010097
Regions
	Nucleotide binding	103 – 109	7	ATP Potential
Amino acid modifications
	Modified residue	33	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	1 – 42	42	Missing in isoform 2 and isoform 3.		VSP_018733
	Alternative sequence	43 – 50	8	Missing in isoform 3.		VSP_041959
	Alternative sequence	168 – 193	26	Missing in isoform 4.		VSP_041960
	Natural variant	13	1	F → L. Ref.13 Corresponds to variant rs11554717 [ dbSNP | Ensembl ].		VAR_066016
	Natural variant	22	1	I → V. Ref.1 Ref.3 Ref.5 Corresponds to variant rs10760502 [ dbSNP | Ensembl ].		VAR_059305
	Natural variant	437	1	V → D. Corresponds to variant rs12686275 [ dbSNP | Ensembl ].		VAR_043929
	Natural variant	466	1	R → 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 accummulation 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 variant	489	1	A → V. Ref.3 Ref.13 Corresponds to variant rs17855900 [ dbSNP | Ensembl ].		VAR_043930
	Natural variant	499	1	S → 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 accummulation 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		VAR_066018
	Natural variant	528	1	S → T. Corresponds to variant rs34354111 [ dbSNP | Ensembl ].		VAR_043931
Experimental info
	Sequence conflict	101	1	V → A in BAG51826. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Mitochondrial) [UniParc]. Last modified October 1, 1996. Version 3. Checksum: 5AF81409F5F77E5C	FASTA	587	64,609
	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
	Isoform 2 (Cytoplasmic) [UniParc]. Checksum: 59650383900A309E	FASTA	545	60,167
	10 20 30 40 50 60 MEYQDAVRML NTLQTNAGYL EQVKRQRGDP QTQLEAMELY LARSGLQVED LDRLNIIHVT 70 80 90 100 110 120 GTKGKGSTCA FTECILRSYG LKTGFFSSPH LVQVRERIRI NGQPISPELF TKYFWRLYHR 130 140 150 160 170 180 LEETKDGSCV SMPPYFRFLT LMAFHVFLQE KVDLAVVEVG IGGAYDCTNI IRKPVVCGVS 190 200 210 220 230 240 SLGIDHTSLL GDTVEKIAWQ KGGIFKQGVP AFTVLQPEGP LAVLRDRAQQ ISCPLYLCPM 250 260 270 280 290 300 LEALEEGGPP LTLGLEGEHQ RSNAALALQL AHCWLQRQDR HGAGEPKASR PGLLWQLPLA 310 320 330 340 350 360 PVFQPTSHMR LGLRNTEWPG RTQVLRRGPL TWYLDGAHTA SSAQACVRWF RQALQGRERP 370 380 390 400 410 420 SGGPEVRVLL FNATGDRDPA ALLKLLQPCQ FDYAVFCPNL TEVSSTGNAD QQNFTVTLDQ 430 440 450 460 470 480 VLLRCLEHQQ HWNHLDEEQA SPDLWSAPSP EPGGSASLLL APHPPHTCSA SSLVFSCISH 490 500 510 520 530 540 ALQWISQGRD PIFQPPSPPK GLLTHPVAHS GASILREAAA IHVLVTGSLH LVGGVLKLLE PALSQ
	Isoform 3 [UniParc]. Checksum: 4FA022E884342D11	FASTA	537	59,174
	10 20 30 40 50 60 MLNTLQTNAG YLEQVKRQRG DPQTQLEAME LYLARSGLQV EDLDRLNIIH VTGTKGKGST 70 80 90 100 110 120 CAFTECILRS YGLKTGFFSS PHLVQVRERI RINGQPISPE LFTKYFWRLY HRLEETKDGS 130 140 150 160 170 180 CVSMPPYFRF LTLMAFHVFL QEKVDLAVVE VGIGGAYDCT NIIRKPVVCG VSSLGIDHTS 190 200 210 220 230 240 LLGDTVEKIA WQKGGIFKQG VPAFTVLQPE GPLAVLRDRA QQISCPLYLC PMLEALEEGG 250 260 270 280 290 300 PPLTLGLEGE HQRSNAALAL QLAHCWLQRQ DRHGAGEPKA SRPGLLWQLP LAPVFQPTSH 310 320 330 340 350 360 MRLGLRNTEW PGRTQVLRRG PLTWYLDGAH TASSAQACVR WFRQALQGRE RPSGGPEVRV 370 380 390 400 410 420 LLFNATGDRD PAALLKLLQP CQFDYAVFCP NLTEVSSTGN ADQQNFTVTL DQVLLRCLEH 430 440 450 460 470 480 QQHWNHLDEE QASPDLWSAP SPEPGGSASL LLAPHPPHTC SASSLVFSCI SHALQWISQG 490 500 510 520 530 RDPIFQPPSP PKGLLTHPVA HSGASILREA AAIHVLVTGS LHLVGGVLKL LEPALSQ
	Isoform 4 [UniParc]. Checksum: 243138601850E090	FASTA	561	61,562
	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 HRLEETKVDL AVVEVGIGGA 190 200 210 220 230 240 YDCTNIIRKP VVCGVSSLGI DHTSLLGDTV EKIAWQKGGI FKQGVPAFTV LQPEGPLAVL 250 260 270 280 290 300 RDRAQQISCP LYLCPMLEAL EEGGPPLTLG LEGEHQRSNA ALALQLAHCW LQRQDRHGAG 310 320 330 340 350 360 EPKASRPGLL WQLPLAPVFQ PTSHMRLGLR NTEWPGRTQV LRRGPLTWYL DGAHTASSAQ 370 380 390 400 410 420 ACVRWFRQAL QGRERPSGGP EVRVLLFNAT GDRDPAALLK LLQPCQFDYA VFCPNLTEVS 430 440 450 460 470 480 STGNADQQNF TVTLDQVLLR CLEHQQHWNH LDEEQASPDL WSAPSPEPGG SASLLLAPHP 490 500 510 520 530 540 PHTCSASSLV FSCISHALQW ISQGRDPIFQ PPSPPKGLLT HPVAHSGASI LREAAAIHVL 550 560 VTGSLHLVGG VLKLLEPALS Q

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
+	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.
IPI	IPI00016745. IPI00759584.
PIR	A46281.
RefSeq	NP_001018088.1. NM_001018078.1. NP_004948.4. NM_004957.4.
UniGene	Hs.335084.
3D structure databases
ProteinModelPortal	Q05932.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000362344.
PTM databases
PhosphoSite	Q05932.
Polymorphism databases
DMDM	1706884.
Proteomic databases
PaxDb	Q05932.
PRIDE	Q05932.
Protocols and materials databases
DNASU	2356.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000373225; ENSP00000362322; ENSG00000136877. ENST00000373247; ENSP00000362344; ENSG00000136877. ENST00000393706; ENSP00000377309; ENSG00000136877.
GeneID	2356.
KEGG	hsa:2356.
UCSC	uc004bsg.1. human.
Organism-specific databases
CTD	2356.
GeneCards	GC09P130556.
HGNC	HGNC:3824. FPGS.
HPA	HPA050488.
MIM	136510. gene+phenotype.
neXtProt	NX_Q05932.
PharmGKB	PA167.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0285.
HOGENOM	HOG000181278.
HOVERGEN	HBG003086.
InParanoid	Q05932.
KO	K01930.
OMA	MEYQDAI.
OrthoDB	EOG4CRKZZ.
PhylomeDB	Q05932.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
UniPathway	UPA00850.
Gene expression databases
ArrayExpress	Q05932.
Bgee	Q05932.
CleanEx	HS_FPGS.
Genevestigator	Q05932.
GermOnline	ENSG00000136877. Homo sapiens.
Family and domain databases
Gene3D	3.40.1190.10. 1 hit. 3.90.190.20. 3 hits.
InterPro	IPR001645. Folylpolyglutamate_synth. IPR018109. Folylpolyglutamate_synth_CS. IPR023600. Folylpolyglutamate_synth_euk. IPR004101. Mur_ligase_C. IPR013221. Mur_ligase_cen. [Graphical view]
PANTHER	PTHR11136. PTHR11136. 1 hit.
PIRSF	PIRSF038895. FPGS. 1 hit.
SUPFAM	SSF53244. Mur_ligase_C. 1 hit. SSF53623. Mur_ligase_cen. 1 hit.
TIGRFAMs	TIGR01499. folC. 1 hit.
PROSITE	PS01011. FOLYLPOLYGLU_SYNT_1. 1 hit. PS01012. FOLYLPOLYGLU_SYNT_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q05932.
ChEMBL	CHEMBL3171.
DrugBank	DB00142. L-Glutamic Acid.
GenomeRNAi	2356.
NextBio	9555.
SOURCE	Search...

Entry information

Entry name

FOLC_HUMAN

Accession

Primary (citable) accession number: Q05932
Secondary accession number(s): B3KPW4 , B7Z2Z3, F5H0K6, Q5JU19, Q5JU22, Q6P2P6

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 131 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.