TYSY_DROME
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 03-AUG-2022, entry version 154.
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 iPTMnet; O76511; -.
DR PaxDb; O76511; -.
DR PRIDE; O76511; -.
DR DNASU; 33499; -.
DR EnsemblMetazoa; FBtr0077679; FBpp0077363; FBgn0024920.
DR EnsemblMetazoa; FBtr0343784; FBpp0310349; FBgn0024920.
DR GeneID; 33499; -.
DR KEGG; dme:Dmel_CG3181; -.
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; KQYLDLC; -.
DR OrthoDB; 1197342at2759; -.
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 tissues.
DR ExpressionAtlas; O76511; baseline and differential.
DR Genevisible; O76511; DM.
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; -; 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 PANTHER; PTHR11548; PTHR11548; 1.
DR Pfam; PF00303; Thymidylat_synt; 1.
DR PRINTS; PR00108; THYMDSNTHASE.
DR SUPFAM; SSF55831; SSF55831; 1.
DR TIGRFAMs; TIGR03284; thym_sym; 1.
DR PROSITE; PS00091; THYMIDYLATE_SYNTHASE; 1.
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
