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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

    Pathwayi: dTTP 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)DescriptionActionsGraphical viewLength
    Binding sitei30dUMPBy similarity1
    Active sitei177NucleophileBy similarity1
    Binding sitei2095,10-methylenetetrahydrofolateBy similarity1
    Binding sitei217dUMPBy similarity1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi157 – 158dUMP; shared with dimeric partnerBy similarity2
    Nucleotide bindingi206 – 209dUMPBy similarity4
    Nucleotide bindingi247 – 249dUMPBy similarity3

    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.
    ReactomeiR-SCE-113510. E2F mediated regulation of DNA replication.
    R-SCE-500753. Pyrimidine biosynthesis.
    R-SCE-69205. 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
    Proteomesi
    • UP000002311 Componenti: Chromosome XV

    Organism-specific databases

    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)DescriptionActionsGraphical viewLength
    ChainiPRO_00001409121 – 304Thymidylate synthaseAdd BLAST304

    Proteomic databases

    MaxQBiP06785.
    PRIDEiP06785.

    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. 16 interactors.
    DIPiDIP-2786N.
    IntActiP06785. 2 interactors.
    MINTiMINT-562757.

    Structurei

    3D structure databases

    ProteinModelPortaliP06785.
    SMRiP06785.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the thymidylate synthase family.Curated

    Phylogenomic databases

    GeneTreeiENSGT00390000014786.
    HOGENOMiHOG000257899.
    InParanoidiP06785.
    KOiK00560.
    OMAiPHKTIAM.
    OrthoDBiEOG092C3QQ6.

    Family and domain databases

    CDDicd00351. TS_Pyrimidine_HMase. 1 hit.
    Gene3Di3.30.572.10. 1 hit.
    HAMAPiMF_00008. Thymidy_synth_bact. 1 hit.
    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)DescriptionActionsGraphical viewLength
    Sequence conflicti34 – 78Missing in CAA99267 (PubMed:9169874).CuratedAdd BLAST45

    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.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi34473. 16 interactors.
    DIPiDIP-2786N.
    IntActiP06785. 2 interactors.
    MINTiMINT-562757.

    Proteomic databases

    MaxQBiP06785.
    PRIDEiP06785.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

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

    Organism-specific databases

    EuPathDBiFungiDB:YOR074C.
    SGDiS000005600. CDC21.

    Phylogenomic databases

    GeneTreeiENSGT00390000014786.
    HOGENOMiHOG000257899.
    InParanoidiP06785.
    KOiK00560.
    OMAiPHKTIAM.
    OrthoDBiEOG092C3QQ6.

    Enzyme and pathway databases

    UniPathwayiUPA00575.
    BioCyciYEAST:YOR074C-MONOMER.
    ReactomeiR-SCE-113510. E2F mediated regulation of DNA replication.
    R-SCE-500753. Pyrimidine biosynthesis.
    R-SCE-69205. G1/S-Specific Transcription.

    Miscellaneous databases

    PROiP06785.

    Family and domain databases

    CDDicd00351. TS_Pyrimidine_HMase. 1 hit.
    Gene3Di3.30.572.10. 1 hit.
    HAMAPiMF_00008. Thymidy_synth_bact. 1 hit.
    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...

    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: November 30, 2016
    This is version 145 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

    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 one 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.