Reviewed, UniProtKB/Swiss-Prot P07245 (C1TC_YEAST)

Names and origin

Protein names

Recommended name:
    C-1-tetrahydrofolate synthase, cytoplasmic
      Short name=C1-THF synthase
Including the following 3 domains:
    1- Recommended name:
            Methylenetetrahydrofolate dehydrogenase
              EC=1.5.1.5
    2- Recommended name:
            Methenyltetrahydrofolate cyclohydrolase
              EC=3.5.4.9
    3- Recommended name:
            Formyltetrahydrofolate synthetase
              EC=6.3.4.3

Gene names

Name:	ADE3
Ordered Locus Names:	YGR204W
ORF Names:	G7733

Organism

Saccharomyces cerevisiae (Baker's yeast) [Complete proteome]

Taxonomic identifier

4932 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces

Protein attributes

Sequence length	946 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Catalytic activity	5,10-methylenetetrahydrofolate + NADP+ = 5,10-methenyltetrahydrofolate + NADPH. 5,10-methenyltetrahydrofolate + H2O = 10-formyltetrahydrofolate. ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate.
Pathway	One-carbon metabolism; tetrahydrofolate pathway.
Subunit structure	Homodimer.
Subcellular location	Cytoplasm. Nucleus. Ref.6
Domain	This trifunctional enzyme consists of two major domains: an N-terminal part containing the methylene-THF dehydrogenase and cyclohydrolase activities and a larger C-terminal part containing formyl-THF synthetase activity.
Miscellaneous	Present with 35600 molecules/cell in log phase SD medium. Ref.7
Sequence similarities	In the N-terminal section; belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family. In the C-terminal section; belongs to the formate--tetrahydrofolate ligase family.

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Histidine biosynthesis Methionine biosynthesis One-carbon metabolism Purine biosynthesis
Cellular component	Cytoplasm Nucleus
Ligand	ATP-binding NADP Nucleotide-binding
Molecular function	Hydrolase Ligase Oxidoreductase
PTM	Phosphoprotein
Technical term	Complete proteome Multifunctional enzyme
Gene Ontology (GO)
Biological process	folic acid and derivative biosynthetic process Inferred from electronic annotation. Source: InterPro histidine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW methionine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW one-carbon compound metabolic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW purine base biosynthetic process Inferred from mutant phenotype. Source: SGD purine nucleotide biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Ref.6 Inferred from direct assay. Source: SGD nucleus Ref.6 Inferred from direct assay. Source: SGD
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW formate-tetrahydrofolate ligase activity Inferred from mutant phenotype. Source: SGD methenyltetrahydrofolate cyclohydrolase activity Inferred from mutant phenotype. Source: SGD methylenetetrahydrofolate dehydrogenase (NADP+) activity Inferred from mutant phenotype. Source: SGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 946	946	C-1-tetrahydrofolate synthase, cytoplasmic		PRO_0000199326
Regions
	Nucleotide binding	169 – 171	3	NADP By similarity
	Nucleotide binding	384 – 391	8	ATP By similarity
	Region	1 – 319	319	Methylenetetrahydrofolate dehydrogenase and cyclohydrolase
	Region	51 – 55	5	Substrate binding By similarity
	Region	98 – 100	3	Substrate binding By similarity
	Region	277 – 281	5	Substrate binding By similarity
	Region	320 – 946	627	Formyltetrahydrofolate synthetase
Sites
	Binding site	194	1	NADP By similarity
Amino acid modifications
	Modified residue	176	1	Phosphoserine Ref.8
	Modified residue	318	1	Phosphothreonine Ref.8
	Modified residue	322	1	Phosphoserine Ref.8
	Modified residue	384	1	Phosphothreonine Ref.8
	Modified residue	894	1	Phosphothreonine Ref.8
Experimental info
	Mutagenesis	11	1	C → S: Almost no effect on activity.
	Mutagenesis	144	1	C → S: Cyclohydrolase activity is reduced 20-fold. Dehydrogenase Km is increased 7-fold.
	Mutagenesis	257	1	C → S: Cyclohydrolase activity is increased 2-fold. Dehydrogenase Km is increased 2-fold.

Sequences

	Sequence		Length	Mass (Da)
	P07245-1 [UniParc]. Last modified April 1, 1988. Version 1. Checksum: BC2897EC380CBA6F	FASTA	946	102,205
	10 20 30 40 50 60 MAGQVLDGKA CAQQFRSNIA NEIKSIQGHV PGFAPNLAII QVGNRPDSAT YVRMKRKAAE 70 80 90 100 110 120 EAGIVANFIH LDESATEFEV LRYVDQLNED PHTHGIIVQL PLPAHLDEDR ITSRVLAEKD 130 140 150 160 170 180 VDGFGPTNIG ELNKKNGHPF FLPCTPKGII ELLHKANVTI EGSRSVVIGR SDIVGSPVAE 190 200 210 220 230 240 LLKSLNSTVT ITHSKTRDIA SYLHDADIVV VAIGQPEFVK GEWFKPRDGT SSDKKTVVID 250 260 270 280 290 300 VGTNYVADPS KKSGFKCVGD VEFNEAIKYV HLITPVPGGV GPMTVAMLMQ NTLIAAKRQM 310 320 330 340 350 360 EESSKPLQIP PLPLKLLTPV PSDIDISRAQ QPKLINQLAQ ELGIYSHELE LYGHYKAKIS 370 380 390 400 410 420 PKVIERLQTR QNGKYILVSG ITPTPLGEGK STTTMGLVQA LTAHLGKPAI ANVRQPSLGP 430 440 450 460 470 480 TLGVKGGAAG GGYSQVIPMD EFNLHLTGDI HAIGAANNLL AAAIDTRMFH ETTQKNDATF 490 500 510 520 530 540 YNRLVPRKNG KRKFTPSMQR RLNRLGIQKT NPDDLTPEEI NKFARLNIDP DTITIKRVVD 550 560 570 580 590 600 INDRMLRQIT IGQAPTEKNH TRVTGFDITV ASELMAILAL SKDLRDMKER IGRVVVAADV 610 620 630 640 650 660 NRSPVTVEDV GCTGALTALL RDAIKPNLMQ TLEGTPVLVH AGPFANISIG ASSVIADRVA 670 680 690 700 710 720 LKLVGTEPEA KTEAGYVVTE AGFDFTMGGE RFFNIKCRSS GLTPNAVVLV ATVRALKSHG 730 740 750 760 770 780 GAPDVKPGQP LPSAYTEENI EFVEKGAANM CKQIANIKQF GVPVVVAINK FETDTEGEIA 790 800 810 820 830 840 AIRKAALEAG AFEAVTSNHW AEGGKGAIDL AKAVIEASNQ PVDFHFLYDV NSSVEDKLTT 850 860 870 880 890 900 IVQKMYGGAA IDILPEAQRK IDMYKEQGFG NLPICIAKTQ YSLSHDATLK GVPTGFTFPI 910 920 930 940 RDVRLSNGAG YLYALAAEIQ TIPGLATYAG YMAVEVDDDG EIDGLF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence of the Saccharomyces cerevisiae ADE3 gene encoding C1-tetrahydrofolate synthase." Staben C., Rabinowitz J.C. J. Biol. Chem. 261:4629-4637(1986) [PubMed: 3514599] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Sequencing of a 17.6 kb segment on the right arm of yeast chromosome VII reveals 12 ORFs, including CCT, ADE3 and TR-I genes, homologues of the yeast PMT and EF1G genes, of the human and bacterial electron-transferring flavoproteins (beta-chain) and of the Escherichia coli phosphoserine phosphohydrolase, and five new ORFs." Guerreiro P., Barreiros T., Soares H., Cyrne L., Maia e Silva A., Rodrigues-Pousada C. Yeast 12:273-280(1996) [PubMed: 8904340] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[3]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome VII." Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J., Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M., Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L., Coblenz A., Coglievina M., Coissac E. , Defoor E., Del Bino S., Delius H., Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P., Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M., Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A., Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K., Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P., Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E., Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K., Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A., Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S., Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M., Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C., Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M., Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M., Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y., Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L., Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D., Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F., Zaccaria P., Zimmermann M., Zollner A., Kleine K. Nature 387:81-84(1997) [PubMed: 9169869] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 96604 / S288c / FY1679.
[4]	"Approaching a complete repository of sequence-verified protein-encoding clones for Saccharomyces cerevisiae." Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F., Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J., Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J. , Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D., LaBaer J. Genome Res. 17:536-543(2007) [PubMed: 17322287] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[5]	"Site-directed mutagenesis of yeast C1-tetrahydrofolate synthase: analysis of an overlapping active site in a multifunctional enzyme." Barlowe C.K., Williams M.E., Rabinowitz J.C., Appling D.R. Biochemistry 28:2099-2106(1989) [PubMed: 2541774] [Abstract] Cited for: MUTAGENESIS.
[6]	"Global analysis of protein localization in budding yeast." Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., Weissman J.S., O'Shea E.K. Nature 425:686-691(2003) [PubMed: 14562095] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
[7]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed: 14562106] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[8]	"A multidimensional chromatography technology for in-depth phosphoproteome analysis." Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H. Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed: 18407956] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-176; THR-318; SER-322; THR-384 AND THR-894, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	M12878 Genomic DNA. Translation: AAA66316.1. Z49133 Genomic DNA. Translation: CAA88997.1. Z72989 Genomic DNA. Translation: CAA97231.1. AY692966 Genomic DNA. Translation: AAT92985.1.
PIR	A29550.
RefSeq	NP_011720.1.
3D structure databases
HSSP	HSSP built from PDB template 1A4I based on UniProtKB P11586.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:3867N.
IntAct	P07245. 38 interactions.
Proteomic databases
PeptideAtlas	P07245.
PRIDE	P07245.
Genome annotation databases
Ensembl	YGR204W. Saccharomyces cerevisiae. [Contig view]
GeneID	853118.
GenomeReviews	Gene locus YGR204W in contig Y13135_GR.
KEGG	sce:YGR204W.
NMPDR	fig|4932.3.peg.2847.
Organism-specific databases
CYGD	YGR204w.
SGD	S000003436. ADE3.
Yeast-GFP	Search...
Phylogenomic databases
HOGENOM	P07245.
OMA	P07245. KYIVVAG.
Enzyme and pathway databases
BRENDA	1.5.1.5. 250. 3.5.4.9. 250. 6.3.4.3. 250.
Gene expression databases
ArrayExpress	P07245.
GermOnline	YGR204W. Saccharomyces cerevisiae.
Family and domain databases
InterPro	IPR000559. For_THF_ligase. IPR016040. NAD(P)-bd_dom. IPR000672. THF_DH/CycHdrlase. [Graphical view]
Gene3D	G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.
Pfam	PF01268. FTHFS. 1 hit. PF00763. THF_DHG_CYH. 1 hit. PF02882. THF_DHG_CYH_C. 1 hit. [Graphical view]
PRINTS	PR00085. THFDHDRGNASE.
ProDom	PD002300. THFDhg/Cyc_hydro. 1 hit. [Graphical view] [Entries sharing at least one domain]
PROSITE	PS00721. FTHFS_1. 1 hit. PS00722. FTHFS_2. 1 hit. PS00766. THF_DHG_CYH_1. 1 hit. PS00767. THF_DHG_CYH_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	973148.

Entry information

Entry name

C1TC_YEAST

Accession

Primary (citable) accession number: P07245

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	April 1, 1988
Last modified:	June 16, 2009
This is version 100 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

FPAP (Fungal Proteome Annotation Project)