ID TYSY_YEAST Reviewed; 304 AA.
AC P06785; D6W2D7; Q12694;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 27-MAR-2024, entry version 184.
DE RecName: Full=Thymidylate synthase;
DE Short=TS;
DE Short=TSase;
DE EC=2.1.1.45;
DE AltName: Full=Cell division cycle protein 21;
DE AltName: Full=Constitutive RNR3 transcription protein 9;
GN Name=CDC21; Synonyms=CRT9, TMP1; OrderedLocusNames=YOR074C;
GN ORFNames=YOR29-25;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3031048; DOI=10.1016/s0021-9258(18)61188-3;
RA Taylor G.R., Lagosky P.A., Storms R.K., Haynes R.H.;
RT "Molecular characterization of the cell cycle-regulated thymidylate
RT synthase gene of Saccharomyces cerevisiae.";
RL J. Biol. Chem. 262:5298-5307(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9133743;
RX DOI=10.1002/(sici)1097-0061(19970330)13:4<379::aid-yea85>3.0.co;2-g;
RA Valens M., Bohn C., Daignan-Fornier B., Dang V.-D., Bolotin-Fukuhara M.;
RT "The sequence of a 54.7 kb fragment of yeast chromosome XV reveals the
RT presence of two tRNAs and 24 new open reading frames.";
RL Yeast 13:379-390(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169874;
RA Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J.,
RA Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A.,
RA Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B.,
RA Dang V.-D., de Haan M., Delius H., Durand P., Fairhead C., Feldmann H.,
RA Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E.,
RA Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U.,
RA Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B.,
RA Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A.,
RA Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C.,
RA Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G.,
RA Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B.,
RA Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B.,
RA Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F.,
RA Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E.,
RA Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I.,
RA Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H.,
RA Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XV.";
RL Nature 387:98-102(1997).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-38.
RX PubMed=3062362; DOI=10.1128/mcb.8.11.4616-4624.1988;
RA McIntosh E.M., Ord R.W., Storms R.K.;
RT "Transcriptional regulation of the cell cycle-dependent thymidylate
RT synthase gene of Saccharomyces cerevisiae.";
RL Mol. Cell. Biol. 8:4616-4624(1988).
RN [6]
RP PROTEIN SEQUENCE OF 1-18, SUBUNIT, CATALYTIC ACTIVITY, FUNCTION, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=7028756; DOI=10.1016/s0021-9258(18)43295-4;
RA Bisson L.F., Thorner J.;
RT "Thymidylate synthetase from Saccharomyces cerevisiae. Purification and
RT enzymic properties.";
RL J. Biol. Chem. 256:12456-12462(1981).
RN [7]
RP FUNCTION.
RX PubMed=17248617; DOI=10.1093/genetics/74.2.267;
RA Hartwell L.H., Mortimer R.K., Culotti J., Culotti M.;
RT "Genetic control of the cell division cycle in yeast: V. Genetic analysis
RT of cdc mutants.";
RL Genetics 74:267-286(1973).
RN [8]
RP FUNCTION.
RX PubMed=4580573; DOI=10.1128/jb.115.3.966-974.1973;
RA Hartwell L.H.;
RT "Three additional genes required for deoxyribonucleic acid synthesis in
RT Saccharomyces cerevisiae.";
RL J. Bacteriol. 115:966-974(1973).
RN [9]
RP FUNCTION.
RX PubMed=334734; DOI=10.1128/jb.132.1.44-50.1977;
RA Bisson L., Thorner J.;
RT "Thymidine 5'-monophosphate-requiring mutants of Saccharomyces cerevisiae
RT are deficient in thymidylate synthetase.";
RL J. Bacteriol. 132:44-50(1977).
RN [10]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=6287238; DOI=10.1128/mcb.2.4.437-442.1982;
RA Taylor G.R., Barclay B.J., Storms R.K., Friesen J.D., Haynes R.H.;
RT "Isolation of the thymidylate synthetase gene (TMP1) by complementation in
RT Saccharomyces cerevisiae.";
RL Mol. Cell. Biol. 2:437-442(1982).
RN [11]
RP INDUCTION.
RX PubMed=3522259; DOI=10.1016/0014-4827(86)90606-3;
RA Johnston L.H., Johnson A.L., Barker D.G.;
RT "The expression in meiosis of genes which are transcribed periodically in
RT the mitotic cell cycle of budding yeast.";
RL Exp. Cell Res. 165:541-549(1986).
RN [12]
RP INDUCTION.
RX PubMed=3020375; DOI=10.1007/bf00331011;
RA McIntosh E.M., Gadsden M.H., Haynes R.H.;
RT "Transcription of genes encoding enzymes involved in DNA synthesis during
RT the cell cycle of Saccharomyces cerevisiae.";
RL Mol. Gen. Genet. 204:363-366(1986).
RN [13]
RP INDUCTION.
RX PubMed=1297653; DOI=10.1242/jcs.1992.supplement_16.11;
RA Moll T., Dirick L., Auer H., Bonkovsky J., Nasmyth K.;
RT "SWI6 is a regulatory subunit of two different cell cycle START-dependent
RT transcription factors in Saccharomyces cerevisiae.";
RL J. Cell Sci. Suppl. 16:87-96(1992).
RN [14]
RP INDUCTION.
RX PubMed=1608451; DOI=10.1038/357508a0;
RA Dirick L., Moll T., Auer H., Nasmyth K.;
RT "A central role for SWI6 in modulating cell cycle Start-specific
RT transcription in yeast.";
RL Nature 357:508-513(1992).
RN [15]
RP INDUCTION.
RX PubMed=1409658; DOI=10.1073/pnas.89.20.9479;
RA Verma R., Smiley J., Andrews B., Campbell J.L.;
RT "Regulation of the yeast DNA replication genes through the Mlu I cell cycle
RT box is dependent on SWI6.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:9479-9483(1992).
RN [16]
RP SUBCELLULAR LOCATION.
RX PubMed=8132557; DOI=10.1016/s0021-9258(17)37199-5;
RA Poon P.P., Storms R.K.;
RT "Thymidylate synthase is localized to the nuclear periphery in the yeast
RT Saccharomyces cerevisiae.";
RL J. Biol. Chem. 269:8341-8347(1994).
CC -!- FUNCTION: Thymidylate synthase required for de novo biosynthesis of
CC pyrimidine deoxyribonucleotides. Required for both nuclear and
CC mitochondrial DNA synthesis. {ECO:0000269|PubMed:17248617,
CC ECO:0000269|PubMed:334734, ECO:0000269|PubMed:4580573,
CC ECO:0000269|PubMed:6287238, ECO:0000269|PubMed:7028756}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + dUMP = 7,8-
CC dihydrofolate + dTMP; Xref=Rhea:RHEA:12104, ChEBI:CHEBI:15636,
CC ChEBI:CHEBI:57451, ChEBI:CHEBI:63528, ChEBI:CHEBI:246422;
CC EC=2.1.1.45; Evidence={ECO:0000269|PubMed:7028756};
CC -!- ACTIVITY REGULATION: Inhibited by 5-fluoro-2'-deoxyuridine 5'-
CC monophosphate (FdUMP). {ECO:0000269|PubMed:6287238}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=5 uM for dUMP {ECO:0000269|PubMed:7028756};
CC KM=70 uM for 5,10-methylene-tetrahydropteroylglutamate
CC {ECO:0000269|PubMed:7028756};
CC pH dependence:
CC Optimum pH is 6.8-7.2. {ECO:0000269|PubMed:7028756};
CC -!- PATHWAY: Pyrimidine metabolism; dTTP biosynthesis.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:7028756}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:8132557}.
CC Note=Localizes to the nuclear periphery.
CC -!- INDUCTION: Transcribed in a periodic manner during the cell cycle with
CC maximal mRNA levels occurring just prior to the onset of DNA
CC replication. The promoter contains 8-base-pair motifs (ACGCGTNA) called
CC the MluI cell-cycle boxes (MCBs), which mediate transcription
CC regulation by SWI6. {ECO:0000269|PubMed:1297653,
CC ECO:0000269|PubMed:1409658, ECO:0000269|PubMed:1608451,
CC ECO:0000269|PubMed:3020375, ECO:0000269|PubMed:3522259}.
CC -!- SIMILARITY: Belongs to the thymidylate synthase family. {ECO:0000305}.
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DR EMBL; J02706; AAA60940.1; -; Genomic_DNA.
DR EMBL; Z70678; CAA94559.1; -; Genomic_DNA.
DR EMBL; Z74982; CAA99267.1; -; Genomic_DNA.
DR EMBL; M29100; AAA35159.1; -; Genomic_DNA.
DR EMBL; BK006948; DAA10853.1; -; Genomic_DNA.
DR PIR; S66957; YXBYT.
DR RefSeq; NP_014717.2; NM_001183493.1.
DR AlphaFoldDB; P06785; -.
DR SMR; P06785; -.
DR BioGRID; 34473; 431.
DR DIP; DIP-2786N; -.
DR IntAct; P06785; 2.
DR MINT; P06785; -.
DR STRING; 4932.YOR074C; -.
DR MaxQB; P06785; -.
DR PaxDb; 4932-YOR074C; -.
DR PeptideAtlas; P06785; -.
DR EnsemblFungi; YOR074C_mRNA; YOR074C; YOR074C.
DR GeneID; 854241; -.
DR KEGG; sce:YOR074C; -.
DR AGR; SGD:S000005600; -.
DR SGD; S000005600; CDC21.
DR VEuPathDB; FungiDB:YOR074C; -.
DR eggNOG; KOG0673; Eukaryota.
DR GeneTree; ENSGT00390000014786; -.
DR HOGENOM; CLU_021669_0_2_1; -.
DR InParanoid; P06785; -.
DR OMA; IVYELLW; -.
DR OrthoDB; 1118873at2759; -.
DR BioCyc; YEAST:YOR074C-MONOMER; -.
DR Reactome; R-SCE-499943; Interconversion of nucleotide di- and triphosphates.
DR UniPathway; UPA00575; -.
DR BioGRID-ORCS; 854241; 1 hit in 10 CRISPR screens.
DR PRO; PR:P06785; -.
DR Proteomes; UP000002311; Chromosome XV.
DR RNAct; P06785; Protein.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0034399; C:nuclear periphery; IDA:SGD.
DR GO; GO:0004799; F:thymidylate synthase activity; IDA:SGD.
DR GO; GO:0006231; P:dTMP biosynthetic process; IMP:SGD.
DR GO; GO:0006235; P:dTTP biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR CDD; cd00351; TS_Pyrimidine_HMase; 1.
DR Gene3D; 3.30.572.10; Thymidylate synthase/dCMP hydroxymethylase domain; 1.
DR HAMAP; MF_00008; Thymidy_synth_bact; 1.
DR InterPro; IPR045097; Thymidate_synth/dCMP_Mease.
DR InterPro; IPR023451; Thymidate_synth/dCMP_Mease_dom.
DR InterPro; IPR036926; Thymidate_synth/dCMP_Mease_sf.
DR InterPro; IPR000398; Thymidylate_synthase.
DR InterPro; IPR020940; Thymidylate_synthase_AS.
DR NCBIfam; TIGR03284; thym_sym; 1.
DR PANTHER; PTHR11548:SF2; THYMIDYLATE SYNTHASE; 1.
DR PANTHER; PTHR11548; THYMIDYLATE SYNTHASE 1; 1.
DR Pfam; PF00303; Thymidylat_synt; 1.
DR PRINTS; PR00108; THYMDSNTHASE.
DR SUPFAM; SSF55831; Thymidylate synthase/dCMP hydroxymethylase; 1.
DR PROSITE; PS00091; THYMIDYLATE_SYNTHASE; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Methyltransferase; Nucleotide biosynthesis;
KW Nucleus; Reference proteome; Transferase.
FT CHAIN 1..304
FT /note="Thymidylate synthase"
FT /id="PRO_0000140912"
FT ACT_SITE 177
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P0A884"
FT BINDING 30
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P0A884"
FT BINDING 157..158
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:P0A884"
FT BINDING 206..209
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P0A884"
FT BINDING 209
FT /ligand="(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:15636"
FT /evidence="ECO:0000250|UniProtKB:P0A884"
FT BINDING 217
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P0A884"
FT BINDING 247..249
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P0A884"
FT CONFLICT 34..78
FT /note="Missing (in Ref. 3; CAA99267)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 304 AA; 35047 MW; 0C514BEDB8574510 CRC64;
MTMDGKNKEE EQYLDLCKRI IDEGEFRPDR TGTGTLSLFA PPQLRFSLRD DTFPLLTTKK
VFTRGIILEL LWFLAGDTDA NLLSEQGVKI WDGNGSREYL DKMGFKDRKV GDLGPVYGFQ
WRHFGAKYKT CDDDYTGQGI DQLKQVIHKL KTNPYDRRII MSAWNPADFD KMALPPCHIF
SQFYVSFPKE GEGSGKPRLS CLLYQRSCDM GLGVPFNIAS YALLTRMIAK VVDMEPGEFI
HTLGDAHVYK DHIDALKEQI TRNPRPFPKL KIKRDVKDID DFKLTDFEIE DYNPHPRIQM
KMSV
//
