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P07245 (C1TC_YEAST) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 147. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
C-1-tetrahydrofolate synthase, cytoplasmic

Short name=C1-THF synthase

Including the following 3 domains:

  1. Methylenetetrahydrofolate dehydrogenase
    EC=1.5.1.5
  2. Methenyltetrahydrofolate cyclohydrolase
    EC=3.5.4.9
  3. Formyltetrahydrofolate synthetase
    EC=6.3.4.3
Gene names
Name:ADE3
Ordered Locus Names:YGR204W
ORF Names:G7733
OrganismSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]
Taxonomic identifier559292 [NCBI]
Taxonomic lineageEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces

Protein attributes

Sequence length946 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Catalytic activity

5,10-methylenetetrahydrofolate + NADP+ = 5,10-methenyltetrahydrofolate + NADPH. HAMAP-Rule MF_01543

5,10-methenyltetrahydrofolate + H2O = 10-formyltetrahydrofolate. HAMAP-Rule MF_01543

ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate. HAMAP-Rule MF_01543

Pathway

One-carbon metabolism; tetrahydrofolate interconversion. HAMAP-Rule MF_01543

Subunit structure

Homodimer.

Subcellular location

Cytoplasm. Nucleus Ref.7.

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. HAMAP-Rule MF_01543

Miscellaneous

Present with 35600 molecules/cell in log phase SD medium.

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 processAmino-acid biosynthesis
Histidine biosynthesis
Methionine biosynthesis
One-carbon metabolism
Purine biosynthesis
   Cellular componentCytoplasm
Nucleus
   LigandATP-binding
NADP
Nucleotide-binding
   Molecular functionHydrolase
Ligase
Oxidoreductase
   PTMPhosphoprotein
   Technical termComplete proteome
Multifunctional enzyme
Reference proteome
Gene Ontology (GO)
   Biological_processfolic acid-containing compound biosynthetic process

Inferred from electronic annotation. Source: InterPro

folic acid-containing compound metabolic process

Inferred from mutant phenotype PubMed 5563870. Source: SGD

histidine biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

methionine biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

purine nucleobase biosynthetic process

Inferred from mutant phenotype PubMed 8464869. Source: SGD

purine nucleotide biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

tetrahydrofolate interconversion

Inferred from electronic annotation. Source: UniProtKB-UniPathway

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

formate-tetrahydrofolate ligase activity

Inferred from mutant phenotype PubMed 8464869. Source: SGD

methenyltetrahydrofolate cyclohydrolase activity

Inferred from mutant phenotype PubMed 8464869. Source: SGD

methylenetetrahydrofolate dehydrogenase (NADP+) activity

Inferred from mutant phenotype PubMed 8464869. Source: SGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 946946C-1-tetrahydrofolate synthase, cytoplasmic HAMAP-Rule MF_01543
PRO_0000199326

Regions

Nucleotide binding169 – 1713NADP By similarity
Nucleotide binding384 – 3918ATP By similarity
Region1 – 319319Methylenetetrahydrofolate dehydrogenase and cyclohydrolase HAMAP-Rule MF_01543
Region51 – 555Substrate binding By similarity
Region98 – 1003Substrate binding By similarity
Region277 – 2815Substrate binding By similarity
Region320 – 946627Formyltetrahydrofolate synthetase HAMAP-Rule MF_01543

Sites

Binding site1941NADP By similarity

Amino acid modifications

Modified residue1761Phosphoserine Ref.10 Ref.11
Modified residue3181Phosphothreonine Ref.11
Modified residue3221Phosphoserine Ref.11

Experimental info

Mutagenesis111C → S: Almost no effect on activity.
Mutagenesis1441C → S: Cyclohydrolase activity is reduced 20-fold. Dehydrogenase Km is increased 7-fold.
Mutagenesis2571C → S: Cyclohydrolase activity is increased 2-fold. Dehydrogenase Km is increased 2-fold.

Sequences

Sequence LengthMass (Da)Tools
P07245 [UniParc].

Last modified April 1, 1988. Version 1.
Checksum: BC2897EC380CBA6F

FASTA946102,205
        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 

« Hide

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: ATCC 204508 / S288c.
[4]Saccharomyces Genome Database
Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases
Cited for: GENOME REANNOTATION.
Strain: ATCC 204508 / S288c.
[5]"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. expand/collapse author list , Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D., LaBaer J.
Genome Res. 17:536-543(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: ATCC 204508 / S288c.
[6]"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] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS.
[7]"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] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
[8]"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] [Europe PMC] [Abstract]
Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[9]"Large-scale phosphorylation analysis of alpha-factor-arrested Saccharomyces cerevisiae."
Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J., Elias J.E., Gygi S.P.
J. Proteome Res. 6:1190-1197(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Strain: ADR376.
[10]"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-176, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Global analysis of Cdk1 substrate phosphorylation sites provides insights into evolution."
Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.
Science 325:1682-1686(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-176; THR-318 AND SER-322, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M12878 Genomic DNA. Translation: AAA66316.1.
Z49133 Genomic DNA. Translation: CAA88997.1.
Z72989 Genomic DNA. Translation: CAA97231.1.
AY692966 Genomic DNA. Translation: AAT92985.1.
BK006941 Genomic DNA. Translation: DAA08297.1.
PIRA29550.
RefSeqNP_011720.3. NM_001181333.3.

3D structure databases

ProteinModelPortalP07245.
SMRP07245. Positions 2-297, 320-946.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid33457. 33 interactions.
DIPDIP-3867N.
IntActP07245. 11 interactions.
MINTMINT-574376.
STRING4932.YGR204W.

Proteomic databases

PaxDbP07245.
PeptideAtlasP07245.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblFungiYGR204W; YGR204W; YGR204W.
GeneID853118.
KEGGsce:YGR204W.

Organism-specific databases

CYGDYGR204w.
SGDS000003436. ADE3.

Phylogenomic databases

eggNOGCOG0190.
GeneTreeENSGT00750000117401.
HOGENOMHOG000040280.
KOK00288.
OMACKIAKES.
OrthoDBEOG7K0ZMJ.

Enzyme and pathway databases

BioCycYEAST:YGR204W-MONOMER.
UniPathwayUPA00193.

Gene expression databases

GenevestigatorP07245.

Family and domain databases

Gene3D3.40.50.300. 2 hits.
3.40.50.720. 1 hit.
HAMAPMF_01543. FTHFS.
MF_01576. THF_DHG_CYH.
InterProIPR000559. Formate_THF_ligase.
IPR020628. Formate_THF_ligase_CS.
IPR016040. NAD(P)-bd_dom.
IPR027417. P-loop_NTPase.
IPR000672. THF_DH/CycHdrlase.
IPR020630. THF_DH/CycHdrlase_cat_dom.
IPR020867. THF_DH/CycHdrlase_CS.
IPR020631. THF_DH/CycHdrlase_NAD-bd_dom.
[Graphical view]
PfamPF01268. FTHFS. 1 hit.
PF00763. THF_DHG_CYH. 1 hit.
PF02882. THF_DHG_CYH_C. 1 hit.
[Graphical view]
PRINTSPR00085. THFDHDRGNASE.
SUPFAMSSF52540. SSF52540. 2 hits.
PROSITEPS00721. 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]
ProtoNetSearch...

Other

NextBio973148.

Entry information

Entry nameC1TC_YEAST
AccessionPrimary (citable) accession number: P07245
Secondary accession number(s): D6VUY6
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: April 1, 1988
Last modified: April 16, 2014
This is version 147 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Relevant documents

Yeast chromosome VII

Yeast (Saccharomyces cerevisiae) chromosome VII: entries and gene names

Yeast

Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways