Reviewed, UniProtKB/Swiss-Prot Q05932 (FOLC_HUMAN)

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) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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	Conversion of folates to polyglutamate derivatives. This allows tissues to concentrate folate at higher levels than in plasma.
Catalytic activity	ATP + tetrahydropteroyl-(gamma-Glu)(n) + L-glutamate = ADP + phosphate + tetrahydropteroyl-(gamma-Glu)(n+1).
Pathway	Cofactor biosynthesis; tetrahydrofolylpolyglutamate biosynthesis.
Subunit structure	Monomer.
Subcellular location	Mitochondrion. Cytoplasm.
Sequence similarities	Belongs to the folylpolyglutamate synthase family.

Ontologies

Keywords
Biological process	One-carbon metabolism
Cellular component	Cytoplasm Mitochondrion
Coding sequence diversity	Alternative initiation Polymorphism
Domain	Transit peptide
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	folic acid and derivative biosynthetic process Inferred from electronic annotation. Source: InterPro nucleobase, nucleoside, nucleotide and nucleic acid metabolic process Ref.5 Traceable author statement. Source: ProtInc one-carbon compound metabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Ref.5 Traceable author statement. Source: ProtInc mitochondrion Ref.5 Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW tetrahydrofolylpolyglutamate synthase activity Ref.5 Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative initiation. [Align] [Select]

Isoform Mitochondrial (identifier: Q05932-1)

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 Cytoplasmic (identifier: Q05932-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-42: Missing.

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 Cytoplasmic.		VSP_018733
	Natural variant	437	1	V → D: dbSNP rs12686275.		VAR_043929
	Natural variant	489	1	A → V: dbSNP rs17855900. Ref.2		VAR_043930
	Natural variant	528	1	S → T: dbSNP rs34354111.		VAR_043931
Experimental info
	Sequence conflict	22	1	I → V in AAH64393. Ref.2
	Sequence conflict	22	1	I → V in AAA85815. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 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 Cytoplasmic. 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

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-489. Tissue: Lung.
[3]	"Alternate splicing and transcription start sites of the human folylpolyglutamate synthetase gene." Chen L., Qi H., Korenberg J., Shane B. Submitted (JUL-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-353.
[4]	"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: 1409616] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 20-587. Tissue: Lymphocyte.
[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: 7721888] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-107, ALTERNATIVE INITIATION. Tissue: Placenta.
[6]	"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: 8521387] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 102-587. Tissue: Placenta.
[7]	"Mammalian folylpoly-gamma-glutamate synthetase. 1. Purification and general properties of the hog liver enzyme." Cichowicz D.J., Shane B. Biochemistry 26:504-512(1987) [PubMed: 3828320] [Abstract] Cited for: CHARACTERIZATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AL162586 Genomic DNA. Translation: CAI39770.1. BC064393 mRNA. Translation: AAH64393.1. U24253, U24252 Genomic DNA. Translation: AAC13871.1. M98045 mRNA. Translation: AAA35852.1. Different initiation. U14939 Genomic DNA. Translation: AAA85815.1. U40868 , U40863, U40864, U40865, U40866, U40867 Genomic DNA. Translation: AAA87568.1.
IPI	IPI00016745. IPI00759584.
PIR	A46281.
RefSeq	NP_001018088.1. NP_004948.4.
UniGene	Hs.335084
3D structure databases
HSSP	HSSP built from PDB template 1FGS based on UniProtKB P15925.
ModBase	Search...
PTM databases
PhosphoSite	Q05932.
Proteomic databases
PRIDE	Q05932.
Genome annotation databases
Ensembl	ENSG00000136877. Homo sapiens. [Contig view]
GeneID	2356.
KEGG	hsa:2356.
UCSC	uc004bsg.1. human.
Organism-specific databases
GeneCards	GC09P129604.
H-InvDB	HIX0008410.
HGNC	HGNC:3824. FPGS.
MIM	136510. gene+phenotype.
PharmGKB	PA167.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q05932.
HOVERGEN	Q05932.
OMA	Q05932. GIDHTFM.
Enzyme and pathway databases
BRENDA	6.3.2.17. 247.
Reactome	REACT_11193. Metabolism of vitamins and cofactors.
Gene expression databases
Bgee	Q05932.
CleanEx	HS_FPGS.
GermOnline	ENSG00000136877. Homo sapiens.
Family and domain databases
InterPro	IPR018109. Folylpolyglutamate_synth_CS. IPR001645. Fpolygl_synthtse. IPR004101. Mur_ligase_C. IPR013221. Mur_ligase_cen. [Graphical view]
Gene3D	G3DSA:3.90.190.20. Mur_ligase_C. 1 hit. G3DSA:3.40.1190.10. Mur_ligase_cen. 1 hit.
PANTHER	PTHR11136. Fpolygl_synthtse. 1 hit.
Pfam	PF02875. Mur_ligase_C. 1 hit. [Graphical view]
TIGRFAMs	TIGR01499. folC. 1 hit.
PROSITE	PS01011. FOLYLPOLYGLU_SYNT_1. 1 hit. PS01012. FOLYLPOLYGLU_SYNT_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00142. L-Glutamic Acid.
NextBio	9555.
SOURCE	Search...

Entry information

Entry name

FOLC_HUMAN

Accession

Primary (citable) accession number: Q05932
Secondary accession number(s): Q5JU22, Q6P2P6

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	October 1, 1996
Last modified:	July 7, 2009
This is version 92 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)