P06785 (TYSY_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Thymidylate synthase
Short name=TS
Short name=TSase
EC=2.1.1.45

Alternative name(s):
Cell division cycle protein 21
Constitutive RNR3 transcription protein 9

Gene names

Name:	CDC21
Synonyms:	CRT9, TMP1
Ordered Locus Names:	YOR074C
ORF Names:	YOR29-25

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Fungi › Dikarya › Ascomycota › saccharomyceta › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces › Saccharomyces cerevisiae

Protein attributes

Sequence length	304 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Thymidylate synthase required for de novo biosynthesis of pyrimidine deoxyribonucleotides. Required for both nuclear and mitochondrial DNA synthesis. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10
Catalytic activity	5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP. Ref.6
Enzyme regulation	Inhibited by 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP). Ref.10
Pathway	Pyrimidine metabolism; dTTP biosynthesis.
Subunit structure	Homodimer. Ref.6
Subcellular location	Nucleus. Note: Localizes to the nuclear periphery. Ref.16
Induction	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. Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15
Sequence similarities	Belongs to the thymidylate synthase family.
Biophysicochemical properties	Kinetic parameters: KM=5 µM for dUMP Ref.6 KM=70 µM for 5,10-methylene-tetrahydropteroylglutamate pH dependence: Optimum pH is 6.8-7.2.

Ontologies

Keywords
Biological process	Nucleotide biosynthesis
Cellular component	Nucleus
Molecular function	Methyltransferase Transferase
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	dTMP biosynthetic process Inferred from electronic annotation. Source: InterPro dTTP biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway
Cellular_component	nucleus Inferred from direct assay Ref.16. Source: SGD
Molecular_function	thymidylate synthase activity Inferred from direct assay Ref.10. Source: SGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 304	304	Thymidylate synthase		PRO_0000140912
Sites
	Active site	177	1	By similarity
Experimental info
	Sequence conflict	34 – 78	45	Missing in CAA99267. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P06785 [UniParc]. Last modified January 1, 1988. Version 1. Checksum: 0C514BEDB8574510	FASTA	304	35,047
	10 20 30 40 50 60 MTMDGKNKEE EQYLDLCKRI IDEGEFRPDR TGTGTLSLFA PPQLRFSLRD DTFPLLTTKK 70 80 90 100 110 120 VFTRGIILEL LWFLAGDTDA NLLSEQGVKI WDGNGSREYL DKMGFKDRKV GDLGPVYGFQ 130 140 150 160 170 180 WRHFGAKYKT CDDDYTGQGI DQLKQVIHKL KTNPYDRRII MSAWNPADFD KMALPPCHIF 190 200 210 220 230 240 SQFYVSFPKE GEGSGKPRLS CLLYQRSCDM GLGVPFNIAS YALLTRMIAK VVDMEPGEFI 250 260 270 280 290 300 HTLGDAHVYK DHIDALKEQI TRNPRPFPKL KIKRDVKDID DFKLTDFEIE DYNPHPRIQM KMSV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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 96604 / S288c / FY1679.
[4]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases 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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
PIR	YXBYT. S66957.
RefSeq	NP_014717.2. NM_001183493.1.
3D structure databases
ProteinModelPortal	P06785.
SMR	P06785. Positions 7-304.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-2786N.
IntAct	P06785. 2 interactions.
MINT	MINT-562757.
STRING	4932.YOR074C.
Proteomic databases
PaxDb	P06785.
PeptideAtlas	P06785.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblFungi	YOR074C; YOR074C; YOR074C.
GeneID	854241.
KEGG	sce:YOR074C.
Organism-specific databases
CYGD	YOR074c.
SGD	S000005600. CDC21.
Phylogenomic databases
eggNOG	COG0207.
GeneTree	ENSGT00390000014786.
HOGENOM	HOG000257899.
KO	K00560.
OMA	DTNVAYL.
OrthoDB	EOG418FX9.
Enzyme and pathway databases
UniPathway	UPA00575.
Gene expression databases
Genevestigator	P06785.
Family and domain databases
Gene3D	3.30.572.10. 1 hit.
InterPro	IPR023451. Thymidate_synth/dCMP_Mease. IPR000398. Thymidylate_synthase. IPR020940. Thymidylate_synthase_AS. [Graphical view]
Pfam	PF00303. Thymidylat_synt. 1 hit. [Graphical view]
PRINTS	PR00108. THYMDSNTHASE.
SUPFAM	SSF55831. Thymidylat_synth_C. 1 hit.
TIGRFAMs	TIGR03284. thym_sym. 1 hit.
PROSITE	PS00091. THYMIDYLATE_SYNTHASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	976141.

Entry information

Entry name

TYSY_YEAST

Accession

Primary (citable) accession number: P06785
Secondary accession number(s): D6W2D7, Q12694

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1988
Last sequence update:	January 1, 1988
Last modified:	April 3, 2013
This is version 117 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program