ID   TYSY_SCHPO              Reviewed;         625 AA.
AC   Q9UTI7;
DT   13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   27-MAR-2024, entry version 138.
DE   RecName: Full=Probable thymidylate synthase;
DE            Short=TS;
DE            Short=TSase;
DE            EC=2.1.1.45;
GN   ORFNames=SPAC15E1.04;
OS   Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC   Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC   Schizosaccharomyces.
OX   NCBI_TaxID=284812;
RN   [1] {ECO:0000312|EMBL:CAB52423.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=972 / ATCC 24843;
RX   PubMed=11859360; DOI=10.1038/nature724;
RA   Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA   Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA   Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA   Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA   Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA   Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA   Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA   Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA   O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA   Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA   Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA   Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA   Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA   Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA   Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA   Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA   Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA   Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA   Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA   Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA   del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA   Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA   Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA   Nurse P.;
RT   "The genome sequence of Schizosaccharomyces pombe.";
RL   Nature 415:871-880(2002).
RN   [2] {ECO:0000305}
RP   SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX   PubMed=16823372; DOI=10.1038/nbt1222;
RA   Matsuyama A., Arai R., Yashiroda Y., Shirai A., Kamata A., Sekido S.,
RA   Kobayashi Y., Hashimoto A., Hamamoto M., Hiraoka Y., Horinouchi S.,
RA   Yoshida M.;
RT   "ORFeome cloning and global analysis of protein localization in the fission
RT   yeast Schizosaccharomyces pombe.";
RL   Nat. Biotechnol. 24:841-847(2006).
CC   -!- FUNCTION: Required for both nuclear and mitochondrial DNA synthesis.
CC       {ECO:0000250|UniProtKB:P06785}.
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:0000250|UniProtKB:P06785};
CC   -!- PATHWAY: Pyrimidine metabolism; dTTP biosynthesis.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16823372}.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the HFCD (homo-
CC       oligomeric flavin containing Cys decarboxylase) superfamily.
CC       {ECO:0000255}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the thymidylate
CC       synthase family. {ECO:0000255}.
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DR   EMBL; CU329670; CAB52423.1; -; Genomic_DNA.
DR   PIR; T37719; T37719.
DR   RefSeq; NP_594305.1; NM_001019728.2.
DR   AlphaFoldDB; Q9UTI7; -.
DR   SMR; Q9UTI7; -.
DR   BioGRID; 279249; 10.
DR   STRING; 284812.Q9UTI7; -.
DR   MoonProt; Q9UTI7; -.
DR   iPTMnet; Q9UTI7; -.
DR   MaxQB; Q9UTI7; -.
DR   PaxDb; 4896-SPAC15E1-04-1; -.
DR   EnsemblFungi; SPAC15E1.04.1; SPAC15E1.04.1:pep; SPAC15E1.04.
DR   GeneID; 2542801; -.
DR   KEGG; spo:SPAC15E1.04; -.
DR   PomBase; SPAC15E1.04; -.
DR   VEuPathDB; FungiDB:SPAC15E1.04; -.
DR   eggNOG; KOG0672; Eukaryota.
DR   eggNOG; KOG0673; Eukaryota.
DR   HOGENOM; CLU_028985_0_0_1; -.
DR   InParanoid; Q9UTI7; -.
DR   OMA; GMAEWRN; -.
DR   PhylomeDB; Q9UTI7; -.
DR   Reactome; R-SPO-499943; Interconversion of nucleotide di- and triphosphates.
DR   UniPathway; UPA00575; -.
DR   PRO; PR:Q9UTI7; -.
DR   Proteomes; UP000002485; Chromosome I.
DR   GO; GO:0005829; C:cytosol; HDA:PomBase.
DR   GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR   GO; GO:0010181; F:FMN binding; IDA:PomBase.
DR   GO; GO:0004633; F:phosphopantothenoylcysteine decarboxylase activity; IDA:PomBase.
DR   GO; GO:0004864; F:protein phosphatase inhibitor activity; IDA:PomBase.
DR   GO; GO:0004799; F:thymidylate synthase activity; IGI:PomBase.
DR   GO; GO:0015937; P:coenzyme A biosynthetic process; IC:PomBase.
DR   GO; GO:0006231; P:dTMP biosynthetic process; IGI:PomBase.
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; 3.40.50.1950; Flavin prenyltransferase-like; 1.
DR   Gene3D; 3.30.572.10; Thymidylate synthase/dCMP hydroxymethylase domain; 1.
DR   HAMAP; MF_00008; Thymidy_synth_bact; 1.
DR   InterPro; IPR036551; Flavin_trans-like.
DR   InterPro; IPR003382; Flavoprotein.
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; PF02441; Flavoprotein; 1.
DR   Pfam; PF00303; Thymidylat_synt; 1.
DR   PRINTS; PR00108; THYMDSNTHASE.
DR   SUPFAM; SSF52507; Homo-oligomeric flavin-containing Cys decarboxylases, HFCD; 1.
DR   SUPFAM; SSF55831; Thymidylate synthase/dCMP hydroxymethylase; 1.
DR   PROSITE; PS00091; THYMIDYLATE_SYNTHASE; 1.
PE   3: Inferred from homology;
KW   Cytoplasm; Methyltransferase; Nucleotide biosynthesis; Reference proteome;
KW   Transferase.
FT   CHAIN           1..625
FT                   /note="Probable thymidylate synthase"
FT                   /id="PRO_0000310825"
FT   REGION          224..323
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        236..258
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        259..323
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        497
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250|UniProtKB:P0A884"
FT   BINDING         350
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         477..478
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         524..527
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         527
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         535
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         565..567
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"
SQ   SEQUENCE   625 AA;  69893 MW;  B3BC6034BF26F61E CRC64;
     MSQPLHARFA TRAVKNPMIL EKERQLTDSK YHILVAATGS VAAIKLTLIV KSLLTYKGVD
     VQVVLTDPAR NFVEKEDLTA LGVNVYNNAD DWKNWDGLEC PITHIELRRW AHLLLIAPLS
     ANTMAKMANG LCDNLLTSLI RAWAPLKPIL LAPAMNTLMW TNPITQEHLS AISRIYKNSE
     FIMPIEKVLA CGDIGMGGMA EWRNIVGRVA DKLQLEQKSV LPNAVKNIDG QDDDSSEQTA
     AFEEYDDDDD DDVDDNEQSN SMIETSANAD ITPKASLLPS TTESSISKDH ETSQAPLGSE
     SVDTQASENV TTKPEPPVPF TSSEYRNTEE EQYLNLIRYI LENGQSRPDR TGTGTRSVFA
     PPQLRFSLRN NTLPLLTTKR VFLRGVLEEL LWFIHGDTNA NHLSEKGIHI WDGNGSREFL
     DSRGLTDRKV GDLGPIYGFQ WRHFGAQYVD CDTDYTNKGV DQLAQVISTL KLNPYDRRII
     LSAWNPLAIP EMALPPCHIF CQFYVSEPCK PGGKPQLSSM MYQRSADMGL GVPFNIASYS
     LLTHMIAHMC GYEAAEFVHV MGDCHIYNDH LEALQTQLER VPKAFPKLFF KRDAKDIGSI
     DSFSVDDFAV EGYNPYGPIK MKMSV
//