ID   TYSY_DROME              Reviewed;         321 AA.
AC   O76511; Q9VQJ3;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   04-MAY-2001, sequence version 2.
DT   27-MAR-2024, entry version 161.
DE   RecName: Full=Thymidylate synthase;
DE            Short=TS;
DE            Short=TSase;
DE            EC=2.1.1.45;
GN   Name=Ts; ORFNames=CG3181;
OS   Drosophila melanogaster (Fruit fly).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC   Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC   Drosophilidae; Drosophila; Sophophora.
OX   NCBI_TaxID=7227;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=Canton-S;
RA   Tsoi S.C.M., Huang S.M., Sander M.;
RT   "Genomic organization of the Drosophlia 23C genetic interval:
RT   identification of 3 genes in the 10Kb region surrounding the RRP1 gene.";
RL   Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Berkeley;
RX   PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA   Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA   Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA   George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA   Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA   Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA   Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA   An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA   Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA   Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA   Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA   Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA   Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA   Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA   Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA   Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA   Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA   Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA   Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA   Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA   Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA   Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA   McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA   Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA   Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA   Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA   Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA   Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA   Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA   Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA   Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA   Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA   Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA   Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA   Venter J.C.;
RT   "The genome sequence of Drosophila melanogaster.";
RL   Science 287:2185-2195(2000).
RN   [3]
RP   GENOME REANNOTATION.
RC   STRAIN=Berkeley;
RX   PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA   Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA   Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA   Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA   Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA   Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA   Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT   "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT   review.";
RL   Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN   [4]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-208 AND SER-210, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=17372656; DOI=10.1039/b617545g;
RA   Bodenmiller B., Mueller L.N., Pedrioli P.G.A., Pflieger D., Juenger M.A.,
RA   Eng J.K., Aebersold R., Tao W.A.;
RT   "An integrated chemical, mass spectrometric and computational strategy for
RT   (quantitative) phosphoproteomics: application to Drosophila melanogaster
RT   Kc167 cells.";
RL   Mol. Biosyst. 3:275-286(2007).
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24; SER-26 AND TYR-39, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RC   TISSUE=Embryo;
RX   PubMed=18327897; DOI=10.1021/pr700696a;
RA   Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT   "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL   J. Proteome Res. 7:1675-1682(2008).
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;
CC   -!- PATHWAY: Pyrimidine metabolism; dTTP biosynthesis.
CC   -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the thymidylate synthase family. {ECO:0000305}.
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DR   EMBL; AF073994; AAC27622.1; -; Genomic_DNA.
DR   EMBL; AE014134; AAF51176.1; -; Genomic_DNA.
DR   RefSeq; NP_001285570.1; NM_001298641.1.
DR   RefSeq; NP_477367.1; NM_058019.4.
DR   AlphaFoldDB; O76511; -.
DR   SMR; O76511; -.
DR   BioGRID; 59719; 1.
DR   DIP; DIP-20012N; -.
DR   IntAct; O76511; 1.
DR   STRING; 7227.FBpp0077363; -.
DR   GlyGen; O76511; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; O76511; -.
DR   PaxDb; 7227-FBpp0077363; -.
DR   DNASU; 33499; -.
DR   EnsemblMetazoa; FBtr0077679; FBpp0077363; FBgn0024920.
DR   EnsemblMetazoa; FBtr0343784; FBpp0310349; FBgn0024920.
DR   GeneID; 33499; -.
DR   KEGG; dme:Dmel_CG3181; -.
DR   AGR; FB:FBgn0024920; -.
DR   CTD; 33499; -.
DR   FlyBase; FBgn0024920; Ts.
DR   VEuPathDB; VectorBase:FBgn0024920; -.
DR   eggNOG; KOG0673; Eukaryota.
DR   HOGENOM; CLU_021669_0_2_1; -.
DR   InParanoid; O76511; -.
DR   OMA; IVYELLW; -.
DR   OrthoDB; 1118873at2759; -.
DR   PhylomeDB; O76511; -.
DR   Reactome; R-DME-499943; Interconversion of nucleotide di- and triphosphates.
DR   UniPathway; UPA00575; -.
DR   BioGRID-ORCS; 33499; 1 hit in 3 CRISPR screens.
DR   GenomeRNAi; 33499; -.
DR   PRO; PR:O76511; -.
DR   Proteomes; UP000000803; Chromosome 2L.
DR   Bgee; FBgn0024920; Expressed in secondary oocyte and 40 other cell types or tissues.
DR   ExpressionAtlas; O76511; baseline and differential.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR   GO; GO:0004799; F:thymidylate synthase activity; IBA:GO_Central.
DR   GO; GO:0006231; P:dTMP biosynthetic process; IBA:GO_Central.
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.
DR   Genevisible; O76511; DM.
PE   1: Evidence at protein level;
KW   Methyltransferase; Nucleotide biosynthesis; Phosphoprotein;
KW   Reference proteome; Transferase.
FT   CHAIN           1..321
FT                   /note="Thymidylate synthase"
FT                   /id="PRO_0000140905"
FT   REGION          1..32
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        201
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250|UniProtKB:P0A884"
FT   BINDING         56
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         181..182
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         223..226
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         226
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         234
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         264..266
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         320
FT                   /ligand="(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate"
FT                   /ligand_id="ChEBI:CHEBI:15636"
FT                   /evidence="ECO:0000250|UniProtKB:P0A884"
FT   MOD_RES         24
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         26
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         39
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         208
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000269|PubMed:17372656"
FT   MOD_RES         210
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:17372656"
FT   CONFLICT        193
FT                   /note="I -> M (in Ref. 1; AAC27622)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   321 AA;  36657 MW;  DCBC920153990CFE CRC64;
     MVLTPTKDGP DQESMPLPAD NGESPSKQQA PVNRDEMHYL DLLRHIIANG EQRMDRTEVG
     TLSVFGSQMR FDMRNSFPLL TTKRVFFRAV AEELLWFVAG KTDAKLLQAK NVHIWDGNSS
     REFLDKMGFT GRAVGDLGPV YGFQWRHFGA QYGTCDDDYS GKGIDQLRQV IDTIRNNPSD
     RRIIMSAWNP LDIPKMALPP CHCLAQFYVS EKRGELSCQL YQRSADMGLG VPFNIASYAL
     LTHMIAHVTG LKPGDFVHTM GDTHVYLNHV EPLKEQLERT PRPFPKLIIK RQVQDIEDFR
     FEDFQIVDYN PHPKIQMDMA V
//