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Protein

Thymidylate synthase

Gene

CDC21

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Thymidylate synthase required for de novo biosynthesis of pyrimidine deoxyribonucleotides. Required for both nuclear and mitochondrial DNA synthesis.5 Publications

Catalytic activityi

5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP.1 Publication

Enzyme regulationi

Inhibited by 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP).1 Publication

Kineticsi

  1. KM=5 µM for dUMP1 Publication
  2. KM=70 µM for 5,10-methylene-tetrahydropteroylglutamate1 Publication

    pH dependencei

    Optimum pH is 6.8-7.2.1 Publication

    Pathway:idTTP biosynthesis

    This protein is involved in the pathway dTTP biosynthesis, which is part of Pyrimidine metabolism.
    View all proteins of this organism that are known to be involved in the pathway dTTP biosynthesis and in Pyrimidine metabolism.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei177 – 1771By similarity

    GO - Molecular functioni

    • thymidylate synthase activity Source: SGD

    GO - Biological processi

    • dTMP biosynthetic process Source: SGD
    • dTTP biosynthetic process Source: UniProtKB-UniPathway
    Complete GO annotation...

    Keywords - Molecular functioni

    Methyltransferase, Transferase

    Keywords - Biological processi

    Nucleotide biosynthesis

    Enzyme and pathway databases

    BioCyciYEAST:YOR074C-MONOMER.
    ReactomeiREACT_303865. E2F mediated regulation of DNA replication.
    REACT_320581. Pyrimidine biosynthesis.
    REACT_345909. G1/S-Specific Transcription.
    UniPathwayiUPA00575.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Thymidylate synthase (EC:2.1.1.45)
    Short name:
    TS
    Short name:
    TSase
    Alternative name(s):
    Cell division cycle protein 21
    Constitutive RNR3 transcription protein 9
    Gene namesi
    Name:CDC21
    Synonyms:CRT9, TMP1
    Ordered Locus Names:YOR074C
    ORF Names:YOR29-25
    OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
    Taxonomic identifieri559292 [NCBI]
    Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
    ProteomesiUP000002311 Componenti: Chromosome XV

    Organism-specific databases

    CYGDiYOR074c.
    EuPathDBiFungiDB:YOR074C.
    SGDiS000005600. CDC21.

    Subcellular locationi

    • Nucleus 1 Publication

    • Note: Localizes to the nuclear periphery.

    GO - Cellular componenti

    • nuclear periphery Source: SGD
    Complete GO annotation...

    Keywords - Cellular componenti

    Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 304304Thymidylate synthasePRO_0000140912Add
    BLAST

    Proteomic databases

    MaxQBiP06785.
    PaxDbiP06785.
    PeptideAtlasiP06785.

    Expressioni

    Inductioni

    Transcribed in a periodic manner during the cell cycle with maximal mRNA levels occurring just prior to the onset of DNA replication. The promoter contains 8-base-pair motifs (ACGCGTNA) called the MluI cell-cycle boxes (MCBs), which mediate transcription regulation by SWI6.5 Publications

    Interactioni

    Subunit structurei

    Homodimer.1 Publication

    Protein-protein interaction databases

    BioGridi34473. 15 interactions.
    DIPiDIP-2786N.
    IntActiP06785. 2 interactions.
    MINTiMINT-562757.

    Structurei

    3D structure databases

    ProteinModelPortaliP06785.
    SMRiP06785. Positions 7-304.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the thymidylate synthase family.Curated

    Phylogenomic databases

    eggNOGiCOG0207.
    GeneTreeiENSGT00390000014786.
    HOGENOMiHOG000257899.
    InParanoidiP06785.
    KOiK00560.
    OMAiNEWADEN.
    OrthoDBiEOG7X6M9G.

    Family and domain databases

    Gene3Di3.30.572.10. 1 hit.
    HAMAPiMF_00008. Thymidy_synth_bact.
    InterProiIPR023451. Thymidate_synth/dCMP_Mease.
    IPR000398. Thymidylate_synthase.
    IPR020940. Thymidylate_synthase_AS.
    [Graphical view]
    PfamiPF00303. Thymidylat_synt. 1 hit.
    [Graphical view]
    PRINTSiPR00108. THYMDSNTHASE.
    SUPFAMiSSF55831. SSF55831. 1 hit.
    TIGRFAMsiTIGR03284. thym_sym. 1 hit.
    PROSITEiPS00091. THYMIDYLATE_SYNTHASE. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P06785-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MTMDGKNKEE EQYLDLCKRI IDEGEFRPDR TGTGTLSLFA PPQLRFSLRD
    60 70 80 90 100
    DTFPLLTTKK VFTRGIILEL LWFLAGDTDA NLLSEQGVKI WDGNGSREYL
    110 120 130 140 150
    DKMGFKDRKV GDLGPVYGFQ WRHFGAKYKT CDDDYTGQGI DQLKQVIHKL
    160 170 180 190 200
    KTNPYDRRII MSAWNPADFD KMALPPCHIF SQFYVSFPKE GEGSGKPRLS
    210 220 230 240 250
    CLLYQRSCDM GLGVPFNIAS YALLTRMIAK VVDMEPGEFI HTLGDAHVYK
    260 270 280 290 300
    DHIDALKEQI TRNPRPFPKL KIKRDVKDID DFKLTDFEIE DYNPHPRIQM

    KMSV
    Length:304
    Mass (Da):35,047
    Last modified:January 1, 1988 - v1
    Checksum:i0C514BEDB8574510
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti34 – 7845Missing in CAA99267 (PubMed:9169874).CuratedAdd
    BLAST

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    J02706 Genomic DNA. Translation: AAA60940.1.
    Z70678 Genomic DNA. Translation: CAA94559.1.
    Z74982 Genomic DNA. Translation: CAA99267.1.
    M29100 Genomic DNA. Translation: AAA35159.1.
    BK006948 Genomic DNA. Translation: DAA10853.1.
    PIRiS66957. YXBYT.
    RefSeqiNP_014717.2. NM_001183493.1.

    Genome annotation databases

    EnsemblFungiiYOR074C; YOR074C; YOR074C.
    GeneIDi854241.
    KEGGisce:YOR074C.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    J02706 Genomic DNA. Translation: AAA60940.1.
    Z70678 Genomic DNA. Translation: CAA94559.1.
    Z74982 Genomic DNA. Translation: CAA99267.1.
    M29100 Genomic DNA. Translation: AAA35159.1.
    BK006948 Genomic DNA. Translation: DAA10853.1.
    PIRiS66957. YXBYT.
    RefSeqiNP_014717.2. NM_001183493.1.

    3D structure databases

    ProteinModelPortaliP06785.
    SMRiP06785. Positions 7-304.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi34473. 15 interactions.
    DIPiDIP-2786N.
    IntActiP06785. 2 interactions.
    MINTiMINT-562757.

    Proteomic databases

    MaxQBiP06785.
    PaxDbiP06785.
    PeptideAtlasiP06785.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblFungiiYOR074C; YOR074C; YOR074C.
    GeneIDi854241.
    KEGGisce:YOR074C.

    Organism-specific databases

    CYGDiYOR074c.
    EuPathDBiFungiDB:YOR074C.
    SGDiS000005600. CDC21.

    Phylogenomic databases

    eggNOGiCOG0207.
    GeneTreeiENSGT00390000014786.
    HOGENOMiHOG000257899.
    InParanoidiP06785.
    KOiK00560.
    OMAiNEWADEN.
    OrthoDBiEOG7X6M9G.

    Enzyme and pathway databases

    UniPathwayiUPA00575.
    BioCyciYEAST:YOR074C-MONOMER.
    ReactomeiREACT_303865. E2F mediated regulation of DNA replication.
    REACT_320581. Pyrimidine biosynthesis.
    REACT_345909. G1/S-Specific Transcription.

    Miscellaneous databases

    NextBioi976141.
    PROiP06785.

    Family and domain databases

    Gene3Di3.30.572.10. 1 hit.
    HAMAPiMF_00008. Thymidy_synth_bact.
    InterProiIPR023451. Thymidate_synth/dCMP_Mease.
    IPR000398. Thymidylate_synthase.
    IPR020940. Thymidylate_synthase_AS.
    [Graphical view]
    PfamiPF00303. Thymidylat_synt. 1 hit.
    [Graphical view]
    PRINTSiPR00108. THYMDSNTHASE.
    SUPFAMiSSF55831. SSF55831. 1 hit.
    TIGRFAMsiTIGR03284. thym_sym. 1 hit.
    PROSITEiPS00091. THYMIDYLATE_SYNTHASE. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Molecular characterization of the cell cycle-regulated thymidylate synthase gene of Saccharomyces cerevisiae."
      Taylor G.R., Lagosky P.A., Storms R.K., Haynes R.H.
      J. Biol. Chem. 262:5298-5307(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "The sequence of a 54.7 kb fragment of yeast chromosome XV reveals the presence of two tRNAs and 24 new open reading frames."
      Valens M., Bohn C., Daignan-Fornier B., Dang V.-D., Bolotin-Fukuhara M.
      Yeast 13:379-390(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    3. "The nucleotide sequence of Saccharomyces cerevisiae chromosome XV."
      Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J., Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A., Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B., Dang V.-D.
      , de Haan M., Delius H., Durand P., Fairhead C., Feldmann H., Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E., Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U., Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B., Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A., Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C., Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G., Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B., Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B., Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F., Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E., Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I., Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H., Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K.
      Nature 387:98-102(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: ATCC 204508 / S288c.
    4. Cited for: GENOME REANNOTATION.
      Strain: ATCC 204508 / S288c.
    5. "Transcriptional regulation of the cell cycle-dependent thymidylate synthase gene of Saccharomyces cerevisiae."
      McIntosh E.M., Ord R.W., Storms R.K.
      Mol. Cell. Biol. 8:4616-4624(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-38.
    6. "Thymidylate synthetase from Saccharomyces cerevisiae. Purification and enzymic properties."
      Bisson L.F., Thorner J.
      J. Biol. Chem. 256:12456-12462(1981) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 1-18, SUBUNIT, CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
    7. "Genetic control of the cell division cycle in yeast: V. Genetic analysis of cdc mutants."
      Hartwell L.H., Mortimer R.K., Culotti J., Culotti M.
      Genetics 74:267-286(1973) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    8. "Three additional genes required for deoxyribonucleic acid synthesis in Saccharomyces cerevisiae."
      Hartwell L.H.
      J. Bacteriol. 115:966-974(1973) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    9. "Thymidine 5'-monophosphate-requiring mutants of Saccharomyces cerevisiae are deficient in thymidylate synthetase."
      Bisson L., Thorner J.
      J. Bacteriol. 132:44-50(1977) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    10. "Isolation of the thymidylate synthetase gene (TMP1) by complementation in Saccharomyces cerevisiae."
      Taylor G.R., Barclay B.J., Storms R.K., Friesen J.D., Haynes R.H.
      Mol. Cell. Biol. 2:437-442(1982) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, ENZYME REGULATION.
    11. "The expression in meiosis of genes which are transcribed periodically in the mitotic cell cycle of budding yeast."
      Johnston L.H., Johnson A.L., Barker D.G.
      Exp. Cell Res. 165:541-549(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION.
    12. "Transcription of genes encoding enzymes involved in DNA synthesis during the cell cycle of Saccharomyces cerevisiae."
      McIntosh E.M., Gadsden M.H., Haynes R.H.
      Mol. Gen. Genet. 204:363-366(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION.
    13. "SWI6 is a regulatory subunit of two different cell cycle START-dependent transcription factors in Saccharomyces cerevisiae."
      Moll T., Dirick L., Auer H., Bonkovsky J., Nasmyth K.
      J. Cell Sci. Suppl. 16:87-96(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION.
    14. "A central role for SWI6 in modulating cell cycle Start-specific transcription in yeast."
      Dirick L., Moll T., Auer H., Nasmyth K.
      Nature 357:508-513(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION.
    15. "Regulation of the yeast DNA replication genes through the Mlu I cell cycle box is dependent on SWI6."
      Verma R., Smiley J., Andrews B., Campbell J.L.
      Proc. Natl. Acad. Sci. U.S.A. 89:9479-9483(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION.
    16. "Thymidylate synthase is localized to the nuclear periphery in the yeast Saccharomyces cerevisiae."
      Poon P.P., Storms R.K.
      J. Biol. Chem. 269:8341-8347(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.

    Entry informationi

    Entry nameiTYSY_YEAST
    AccessioniPrimary (citable) accession number: P06785
    Secondary accession number(s): D6W2D7, Q12694
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 1, 1988
    Last sequence update: January 1, 1988
    Last modified: July 22, 2015
    This is version 134 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programFungal Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. SIMILARITY comments
      Index of protein domains and families
    3. Yeast
      Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
    4. Yeast chromosome XV
      Yeast (Saccharomyces cerevisiae) chromosome XV: entries and gene names

    External Data

    Dasty 3

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.