TYSY_HUMAN
ID TYSY_HUMAN Reviewed; 313 AA.
AC P04818; Q8WYK3; Q8WYK4;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 226.
DE RecName: Full=Thymidylate synthase {ECO:0000305};
DE Short=TS;
DE Short=TSase;
DE EC=2.1.1.45 {ECO:0000269|PubMed:11278511};
GN Name=TYMS {ECO:0000312|HGNC:HGNC:12441}; Synonyms=TS; ORFNames=OK/SW-cl.29;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2987839; DOI=10.1093/nar/13.6.2035;
RA Takeishi K., Kaneda S., Ayusawa D., Shimizu K., Gotoh O., Seno T.;
RT "Nucleotide sequence of a functional cDNA for human thymidylate synthase.";
RL Nucleic Acids Res. 13:2035-2043(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2243092; DOI=10.1016/s0021-9258(17)30501-x;
RA Kaneda S., Nalbantoglu J., Takeishi K., Shimizu K., Gotoh O., Seno T.,
RA Ayusawa D.;
RT "Structural and functional analysis of the human thymidylate synthase
RT gene.";
RL J. Biol. Chem. 265:20277-20284(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), AND ALTERNATIVE SPLICING.
RX PubMed=12706868; DOI=10.1016/s0304-3835(03)00005-3;
RA Hisatomi H., Tanemura H., Iizuka T., Katsumata K., Nagao K., Sumida H.,
RA Udagawa H., Hikiji K.;
RT "Differential alternative splicing expressions of thymidylate synthase
RT isoforms.";
RL Cancer Lett. 193:127-131(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon adenocarcinoma;
RA Shichijo S., Itoh K.;
RT "Identification of immuno-peptidmics that are recognized by tumor-reactive
RT CTL generated from TIL of colon cancer patients.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow, Placenta, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE OF 1-68.
RX PubMed=2532645; DOI=10.1093/oxfordjournals.jbchem.a122898;
RA Takeishi K., Kaneda S., Ayusawa D., Shimizu K., Gotoh O., Seno T.;
RT "Human thymidylate synthase gene: isolation of phage clones which cover a
RT functionally active gene and structural analysis of the region upstream
RT from the translation initiation codon.";
RL J. Biochem. 106:575-583(1989).
RN [9]
RP PROTEIN SEQUENCE OF 2-25.
RX PubMed=3839505; DOI=10.1093/oxfordjournals.jbchem.a135125;
RA Shimizu K., Ayusawa D., Takeishi K., Seno T.;
RT "Purification and NH2-terminal amino acid sequence of human thymidylate
RT synthase in an overproducing transformant of mouse FM3A cells.";
RL J. Biochem. 97:845-850(1985).
RN [10]
RP PROTEIN SEQUENCE OF 2-10.
RX PubMed=2656695; DOI=10.1016/s0021-9258(18)60506-x;
RA Davisson V.J., Sirawaraporn W., Santi D.V.;
RT "Expression of human thymidylate synthase in Escherichia coli.";
RL J. Biol. Chem. 264:9145-9148(1989).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-114, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21876188; DOI=10.1073/pnas.1103623108;
RA Anderson D.D., Quintero C.M., Stover P.J.;
RT "Identification of a de novo thymidylate biosynthesis pathway in mammalian
RT mitochondria.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:15163-15168(2011).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-114, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [16]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-287; LYS-292 AND LYS-308, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
RX PubMed=8845352; DOI=10.1021/bi00050a007;
RA Schiffer C.A., Clifton I.J., Davisson V.J., Santi D.V., Stroud R.M.;
RT "Crystal structure of human thymidylate synthase: a structural mechanism
RT for guiding substrates into the active site.";
RL Biochemistry 34:16279-16287(1995).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
RX PubMed=11329255; DOI=10.1021/bi002413i;
RA Phan J., Koli S., Minor W., Dunlap R.B., Berger S.H., Lebioda L.;
RT "Human thymidylate synthase is in the closed conformation when complexed
RT with dUMP and raltitrexed, an antifolate drug.";
RL Biochemistry 40:1897-1902(2001).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=11278511; DOI=10.1074/jbc.m009493200;
RA Phan J., Steadman D.J., Koli S., Ding W.C., Minor W., Dunlap R.B.,
RA Berger S.H., Lebioda L.;
RT "Structure of human thymidylate synthase suggests advantages of
RT chemotherapy with noncompetitive inhibitors.";
RL J. Biol. Chem. 276:14170-14177(2001).
CC -!- FUNCTION: Catalyzes the reductive methylation of 2'-deoxyuridine 5'-
CC monophosphate (dUMP) to thymidine 5'-monophosphate (dTMP), using the
CC cosubstrate, 5,10- methylenetetrahydrofolate (CH2H4folate) as a 1-
CC carbon donor and reductant and contributes to the de novo mitochondrial
CC thymidylate biosynthesis pathway. {ECO:0000269|PubMed:11278511,
CC ECO:0000269|PubMed:21876188}.
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:11278511};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12105;
CC Evidence={ECO:0000305|PubMed:11278511};
CC -!- PATHWAY: Pyrimidine metabolism; dTTP biosynthesis.
CC {ECO:0000305|PubMed:11278511}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P45352}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21876188}. Cytoplasm
CC {ECO:0000269|PubMed:21876188}. Mitochondrion
CC {ECO:0000269|PubMed:21876188}. Mitochondrion matrix
CC {ECO:0000269|PubMed:21876188}. Mitochondrion inner membrane
CC {ECO:0000269|PubMed:21876188}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P04818-1; Sequence=Displayed;
CC Name=2; Synonyms=delta4;
CC IsoId=P04818-2; Sequence=VSP_047746;
CC Name=3; Synonyms=delta2+3;
CC IsoId=P04818-3; Sequence=VSP_047745;
CC -!- MISCELLANEOUS: [Isoform 2]: Expressed both in normal and cancerous
CC tissues. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: Expressed only in cancerous tissues.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the thymidylate synthase family. {ECO:0000305}.
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DR EMBL; X02308; CAA26178.1; -; mRNA.
DR EMBL; D00596; BAA00472.1; -; Genomic_DNA.
DR EMBL; AB077207; BAB83676.1; -; mRNA.
DR EMBL; AB077208; BAB83677.1; -; mRNA.
DR EMBL; AB062290; BAB93473.1; -; mRNA.
DR EMBL; AP001178; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471113; EAX01716.1; -; Genomic_DNA.
DR EMBL; CH471113; EAX01720.1; -; Genomic_DNA.
DR EMBL; BC002567; AAH02567.1; -; mRNA.
DR EMBL; BC013919; AAH13919.1; -; mRNA.
DR EMBL; BC083512; AAH83512.1; -; mRNA.
DR EMBL; D00517; BAA00404.1; -; Genomic_DNA.
DR CCDS; CCDS11821.1; -. [P04818-1]
DR CCDS; CCDS86658.1; -. [P04818-2]
DR CCDS; CCDS86659.1; -. [P04818-3]
DR PIR; A23047; YXHUT.
DR RefSeq; NP_001062.1; NM_001071.2. [P04818-1]
DR PDB; 1HVY; X-ray; 1.90 A; A/B/C/D=26-313.
DR PDB; 1HW3; X-ray; 2.00 A; A=1-313.
DR PDB; 1HW4; X-ray; 2.06 A; A=1-313.
DR PDB; 1HZW; X-ray; 2.00 A; A/B=1-313.
DR PDB; 1I00; X-ray; 2.50 A; A/B=1-313.
DR PDB; 1JU6; X-ray; 2.89 A; A/B/C/D=1-313.
DR PDB; 1JUJ; X-ray; 3.00 A; A/B/C/D=1-313.
DR PDB; 1YPV; X-ray; 1.80 A; A=1-313.
DR PDB; 2ONB; X-ray; 2.70 A; A=1-313.
DR PDB; 2RD8; X-ray; 2.50 A; A/B=1-313.
DR PDB; 2RDA; X-ray; 2.67 A; A/B/C/D/E/F=1-313.
DR PDB; 3EAW; X-ray; 1.86 A; X=1-313.
DR PDB; 3EBU; X-ray; 2.05 A; A=1-313.
DR PDB; 3ED7; X-ray; 1.56 A; A=26-313.
DR PDB; 3EDW; X-ray; 1.75 A; X=1-313.
DR PDB; 3EF9; X-ray; 3.20 A; A=1-313.
DR PDB; 3EGY; X-ray; 2.18 A; X=1-313.
DR PDB; 3EHI; X-ray; 2.00 A; X=1-313.
DR PDB; 3EJL; X-ray; 3.20 A; A/B/C/D=1-313.
DR PDB; 3GG5; X-ray; 2.77 A; A/B/C/D=1-313.
DR PDB; 3GH0; X-ray; 1.56 A; A=1-313.
DR PDB; 3GH2; X-ray; 1.75 A; X=1-313.
DR PDB; 3H9K; X-ray; 2.65 A; A/B/C/D/E=1-313.
DR PDB; 3HB8; X-ray; 2.74 A; A/B/C/D/E=1-313.
DR PDB; 3N5E; X-ray; 2.26 A; A/B=1-313.
DR PDB; 3N5G; X-ray; 2.27 A; A=1-313.
DR PDB; 3OB7; X-ray; 2.75 A; A/B/C/D/E=1-313.
DR PDB; 4E28; X-ray; 2.30 A; A=1-313.
DR PDB; 4FGT; X-ray; 2.00 A; A=1-311.
DR PDB; 4G2O; X-ray; 2.25 A; X=1-313.
DR PDB; 4G6W; X-ray; 2.30 A; X=1-313.
DR PDB; 4GD7; X-ray; 2.29 A; A=1-313.
DR PDB; 4GYH; X-ray; 3.00 A; A=1-313.
DR PDB; 4H1I; X-ray; 3.10 A; A/B/C/D=1-313.
DR PDB; 4JEF; X-ray; 2.31 A; A=26-311.
DR PDB; 4KPW; X-ray; 2.03 A; A=1-313.
DR PDB; 4O1U; X-ray; 2.26 A; A/B=1-313.
DR PDB; 4O1X; X-ray; 2.32 A; A/B/C/D=1-313.
DR PDB; 4UP1; X-ray; 2.99 A; A/B/C/D=1-313.
DR PDB; 5HS3; X-ray; 3.10 A; A/B/C/D/E/F=26-313.
DR PDB; 5WRN; X-ray; 2.39 A; A/B/C/D/E/F=26-313.
DR PDB; 5X4W; X-ray; 2.10 A; A=1-313.
DR PDB; 5X4X; X-ray; 2.31 A; A=1-313.
DR PDB; 5X4Y; X-ray; 2.20 A; A=1-313.
DR PDB; 5X5A; X-ray; 2.39 A; A/B/C/D/E/F=26-313.
DR PDB; 5X5D; X-ray; 2.00 A; A/B/C/D/E/F=26-313.
DR PDB; 5X5Q; X-ray; 2.79 A; A/B/C/D/E/F=26-313.
DR PDB; 5X66; X-ray; 1.99 A; A/B/C/D/E/F=26-313.
DR PDB; 5X67; X-ray; 2.13 A; A/B=26-313.
DR PDB; 5X69; X-ray; 2.69 A; A/B/C/D/E/F=26-313.
DR PDB; 6OJU; X-ray; 2.88 A; A/B/C/D=26-313.
DR PDB; 6OJV; X-ray; 2.59 A; A/B/C/D=26-313.
DR PDB; 6PF3; X-ray; 2.39 A; A/B/C/D=26-313.
DR PDB; 6PF4; X-ray; 2.85 A; A/B/C/D=26-313.
DR PDB; 6PF5; X-ray; 2.39 A; A/B/C/D=26-313.
DR PDB; 6PF6; X-ray; 2.50 A; A/B/C/D=26-313.
DR PDB; 6QXG; X-ray; 2.08 A; A/B/C=1-313.
DR PDB; 6QXH; X-ray; 2.04 A; A/B/C=1-313.
DR PDB; 6QYQ; X-ray; 2.25 A; A/B/C/D=1-313.
DR PDB; 6R2E; X-ray; 2.55 A; A/B/C/D/E/F/G/H=1-313.
DR PDB; 6ZXO; X-ray; 2.60 A; A/B/C/D/E/F=1-313.
DR PDBsum; 1HVY; -.
DR PDBsum; 1HW3; -.
DR PDBsum; 1HW4; -.
DR PDBsum; 1HZW; -.
DR PDBsum; 1I00; -.
DR PDBsum; 1JU6; -.
DR PDBsum; 1JUJ; -.
DR PDBsum; 1YPV; -.
DR PDBsum; 2ONB; -.
DR PDBsum; 2RD8; -.
DR PDBsum; 2RDA; -.
DR PDBsum; 3EAW; -.
DR PDBsum; 3EBU; -.
DR PDBsum; 3ED7; -.
DR PDBsum; 3EDW; -.
DR PDBsum; 3EF9; -.
DR PDBsum; 3EGY; -.
DR PDBsum; 3EHI; -.
DR PDBsum; 3EJL; -.
DR PDBsum; 3GG5; -.
DR PDBsum; 3GH0; -.
DR PDBsum; 3GH2; -.
DR PDBsum; 3H9K; -.
DR PDBsum; 3HB8; -.
DR PDBsum; 3N5E; -.
DR PDBsum; 3N5G; -.
DR PDBsum; 3OB7; -.
DR PDBsum; 4E28; -.
DR PDBsum; 4FGT; -.
DR PDBsum; 4G2O; -.
DR PDBsum; 4G6W; -.
DR PDBsum; 4GD7; -.
DR PDBsum; 4GYH; -.
DR PDBsum; 4H1I; -.
DR PDBsum; 4JEF; -.
DR PDBsum; 4KPW; -.
DR PDBsum; 4O1U; -.
DR PDBsum; 4O1X; -.
DR PDBsum; 4UP1; -.
DR PDBsum; 5HS3; -.
DR PDBsum; 5WRN; -.
DR PDBsum; 5X4W; -.
DR PDBsum; 5X4X; -.
DR PDBsum; 5X4Y; -.
DR PDBsum; 5X5A; -.
DR PDBsum; 5X5D; -.
DR PDBsum; 5X5Q; -.
DR PDBsum; 5X66; -.
DR PDBsum; 5X67; -.
DR PDBsum; 5X69; -.
DR PDBsum; 6OJU; -.
DR PDBsum; 6OJV; -.
DR PDBsum; 6PF3; -.
DR PDBsum; 6PF4; -.
DR PDBsum; 6PF5; -.
DR PDBsum; 6PF6; -.
DR PDBsum; 6QXG; -.
DR PDBsum; 6QXH; -.
DR PDBsum; 6QYQ; -.
DR PDBsum; 6R2E; -.
DR PDBsum; 6ZXO; -.
DR AlphaFoldDB; P04818; -.
DR SMR; P04818; -.
DR BioGRID; 113149; 83.
DR IntAct; P04818; 16.
DR MINT; P04818; -.
DR STRING; 9606.ENSP00000315644; -.
DR BindingDB; P04818; -.
DR ChEMBL; CHEMBL1952; -.
DR DrugBank; DB03541; 10-Propargyl-5,8-Dideazafolic Acid.
DR DrugBank; DB07577; 2,4-Diamino-5-phenyl-6-ethylpyrimidine.
DR DrugBank; DB08734; 6,6-DIMETHYL-1-[3-(2,4,5-TRICHLOROPHENOXY)PROPOXY]-1,6-DIHYDRO-1,3,5-TRIAZINE-2,4-DIAMINE.
DR DrugBank; DB05308; ANX-510.
DR DrugBank; DB01101; Capecitabine.
DR DrugBank; DB03800; Deoxyuridine monophosphate.
DR DrugBank; DB00322; Floxuridine.
DR DrugBank; DB00544; Fluorouracil.
DR DrugBank; DB00441; Gemcitabine.
DR DrugBank; DB00563; Methotrexate.
DR DrugBank; DB08479; N-(3,5-dimethoxyphenyl)imidodicarbonimidic diamide.
DR DrugBank; DB08478; N-[2-Chloro-5-(trifluoromethyl)phenyl]imidodicarbonimidic diamide.
DR DrugBank; DB05457; OSI-7904L.
DR DrugBank; DB00642; Pemetrexed.
DR DrugBank; DB06813; Pralatrexate.
DR DrugBank; DB00293; Raltitrexed.
DR DrugBank; DB04530; S,S-(2-Hydroxyethyl)Thiocysteine.
DR DrugBank; DB09256; Tegafur.
DR DrugBank; DB09327; Tegafur-uracil.
DR DrugBank; DB05116; Thymectacin.
DR DrugBank; DB01643; Thymidine monophosphate.
DR DrugBank; DB00432; Trifluridine.
DR DrugCentral; P04818; -.
DR GuidetoPHARMACOLOGY; 2642; -.
DR MoonProt; P04818; -.
DR GlyGen; P04818; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P04818; -.
DR MetOSite; P04818; -.
DR PhosphoSitePlus; P04818; -.
DR BioMuta; TYMS; -.
DR DMDM; 136611; -.
DR EPD; P04818; -.
DR jPOST; P04818; -.
DR MassIVE; P04818; -.
DR PaxDb; P04818; -.
DR PeptideAtlas; P04818; -.
DR PRIDE; P04818; -.
DR ProteomicsDB; 51747; -. [P04818-1]
DR ProteomicsDB; 75165; -.
DR ProteomicsDB; 75166; -.
DR TopDownProteomics; P04818-1; -. [P04818-1]
DR Antibodypedia; 3461; 1226 antibodies from 41 providers.
DR DNASU; 7298; -.
DR Ensembl; ENST00000323224.7; ENSP00000314727.7; ENSG00000176890.16. [P04818-2]
DR Ensembl; ENST00000323250.9; ENSP00000314902.5; ENSG00000176890.16. [P04818-3]
DR Ensembl; ENST00000323274.15; ENSP00000315644.10; ENSG00000176890.16. [P04818-1]
DR GeneID; 7298; -.
DR KEGG; hsa:7298; -.
DR MANE-Select; ENST00000323274.15; ENSP00000315644.10; NM_001071.4; NP_001062.1.
DR UCSC; uc010dkb.2; human. [P04818-1]
DR CTD; 7298; -.
DR DisGeNET; 7298; -.
DR GeneCards; TYMS; -.
DR HGNC; HGNC:12441; TYMS.
DR HPA; ENSG00000176890; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 188350; gene.
DR neXtProt; NX_P04818; -.
DR OpenTargets; ENSG00000176890; -.
DR Orphanet; 240839; Prediction of 5-fluorouracil toxicity.
DR PharmGKB; PA359; -.
DR VEuPathDB; HostDB:ENSG00000176890; -.
DR eggNOG; KOG0673; Eukaryota.
DR GeneTree; ENSGT00390000014786; -.
DR HOGENOM; CLU_021669_0_2_1; -.
DR InParanoid; P04818; -.
DR OMA; KQYLDLC; -.
DR PhylomeDB; P04818; -.
DR TreeFam; TF353027; -.
DR BioCyc; MetaCyc:HS11096-MON; -.
DR BRENDA; 2.1.1.45; 2681.
DR PathwayCommons; P04818; -.
DR Reactome; R-HSA-499943; Interconversion of nucleotide di- and triphosphates.
DR Reactome; R-HSA-69205; G1/S-Specific Transcription.
DR SABIO-RK; P04818; -.
DR SignaLink; P04818; -.
DR SIGNOR; P04818; -.
DR UniPathway; UPA00575; -.
DR BioGRID-ORCS; 7298; 314 hits in 1100 CRISPR screens.
DR ChiTaRS; TYMS; human.
DR EvolutionaryTrace; P04818; -.
DR GeneWiki; Thymidylate_synthase; -.
DR GenomeRNAi; 7298; -.
DR Pharos; P04818; Tclin.
DR PRO; PR:P04818; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; P04818; protein.
DR Bgee; ENSG00000176890; Expressed in ventricular zone and 182 other tissues.
DR ExpressionAtlas; P04818; baseline and differential.
DR Genevisible; P04818; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005542; F:folic acid binding; IC:BHF-UCL.
DR GO; GO:0000900; F:mRNA regulatory element binding translation repressor activity; IDA:CAFA.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:1990825; F:sequence-specific mRNA binding; IDA:CAFA.
DR GO; GO:0004799; F:thymidylate synthase activity; IDA:CAFA.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0051216; P:cartilage development; IEA:Ensembl.
DR GO; GO:0007623; P:circadian rhythm; IEA:Ensembl.
DR GO; GO:0048589; P:developmental growth; IEA:Ensembl.
DR GO; GO:0071897; P:DNA biosynthetic process; IC:BHF-UCL.
DR GO; GO:0006231; P:dTMP biosynthetic process; IDA:CAFA.
DR GO; GO:0006235; P:dTTP biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0060574; P:intestinal epithelial cell maturation; IEA:Ensembl.
DR GO; GO:0097421; P:liver regeneration; IEA:Ensembl.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0017148; P:negative regulation of translation; IDA:CAFA.
DR GO; GO:0034097; P:response to cytokine; IEA:Ensembl.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0051593; P:response to folic acid; IEA:Ensembl.
DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR GO; GO:0046683; P:response to organophosphorus; IEP:UniProtKB.
DR GO; GO:0032570; P:response to progesterone; IEA:Ensembl.
DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl.
DR GO; GO:0033189; P:response to vitamin A; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0035999; P:tetrahydrofolate interconversion; IDA:BHF-UCL.
DR GO; GO:0019860; P:uracil metabolic process; IEA:Ensembl.
DR CDD; cd00351; TS_Pyrimidine_HMase; 1.
DR DisProt; DP00073; -.
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 3D-structure; Alternative splicing; Cytoplasm; Direct protein sequencing;
KW Isopeptide bond; Membrane; Methyltransferase; Mitochondrion;
KW Mitochondrion inner membrane; Nucleotide biosynthesis; Nucleus;
KW Phosphoprotein; Reference proteome; Transferase; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:2656695,
FT ECO:0000269|PubMed:3839505"
FT CHAIN 2..313
FT /note="Thymidylate synthase"
FT /id="PRO_0000140901"
FT REGION 1..28
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 195
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P0A884"
FT BINDING 50
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 175..176
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:P45352"
FT BINDING 195..196
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:P45352"
FT BINDING 215..218
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:P45352"
FT BINDING 218
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 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 256..258
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:P45352"
FT BINDING 312
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 114
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT CROSSLNK 287
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 292
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 308
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 69..151
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12706868"
FT /id="VSP_047745"
FT VAR_SEQ 152..185
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12706868"
FT /id="VSP_047746"
FT HELIX 30..43
FT /evidence="ECO:0007829|PDB:3ED7"
FT STRAND 45..48
FT /evidence="ECO:0007829|PDB:3ED7"
FT STRAND 50..52
FT /evidence="ECO:0007829|PDB:1YPV"
FT STRAND 54..66
FT /evidence="ECO:0007829|PDB:3ED7"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:3EBU"
FT TURN 75..78
FT /evidence="ECO:0007829|PDB:3ED7"
FT HELIX 81..92
FT /evidence="ECO:0007829|PDB:3ED7"
FT HELIX 98..101
FT /evidence="ECO:0007829|PDB:3ED7"
FT TURN 103..105
FT /evidence="ECO:0007829|PDB:1HVY"
FT TURN 108..110
FT /evidence="ECO:0007829|PDB:1HZW"
FT HELIX 111..113
FT /evidence="ECO:0007829|PDB:1HVY"
FT HELIX 117..120
FT /evidence="ECO:0007829|PDB:3ED7"
FT HELIX 123..127
FT /evidence="ECO:0007829|PDB:3ED7"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:6OJU"
FT TURN 132..134
FT /evidence="ECO:0007829|PDB:4E28"
FT HELIX 136..141
FT /evidence="ECO:0007829|PDB:3ED7"
FT STRAND 149..151
FT /evidence="ECO:0007829|PDB:3ED7"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:3EHI"
FT HELIX 160..170
FT /evidence="ECO:0007829|PDB:3ED7"
FT STRAND 178..181
FT /evidence="ECO:0007829|PDB:3ED7"
FT HELIX 184..186
FT /evidence="ECO:0007829|PDB:3ED7"
FT TURN 187..189
FT /evidence="ECO:0007829|PDB:3ED7"
FT STRAND 190..192
FT /evidence="ECO:0007829|PDB:3ED7"
FT STRAND 196..204
FT /evidence="ECO:0007829|PDB:3ED7"
FT STRAND 207..218
FT /evidence="ECO:0007829|PDB:3ED7"
FT TURN 219..221
FT /evidence="ECO:0007829|PDB:3ED7"
FT HELIX 222..241
FT /evidence="ECO:0007829|PDB:3ED7"
FT STRAND 244..258
FT /evidence="ECO:0007829|PDB:3ED7"
FT HELIX 259..261
FT /evidence="ECO:0007829|PDB:3ED7"
FT HELIX 262..268
FT /evidence="ECO:0007829|PDB:3ED7"
FT STRAND 278..281
FT /evidence="ECO:0007829|PDB:3ED7"
FT HELIX 288..290
FT /evidence="ECO:0007829|PDB:3ED7"
FT HELIX 293..295
FT /evidence="ECO:0007829|PDB:3ED7"
FT STRAND 296..300
FT /evidence="ECO:0007829|PDB:3ED7"
SQ SEQUENCE 313 AA; 35716 MW; 148D377F19915B6A CRC64;
MPVAGSELPR RPLPPAAQER DAEPRPPHGE LQYLGQIQHI LRCGVRKDDR TGTGTLSVFG
MQARYSLRDE FPLLTTKRVF WKGVLEELLW FIKGSTNAKE LSSKGVKIWD ANGSRDFLDS
LGFSTREEGD LGPVYGFQWR HFGAEYRDME SDYSGQGVDQ LQRVIDTIKT NPDDRRIIMC
AWNPRDLPLM ALPPCHALCQ FYVVNSELSC QLYQRSGDMG LGVPFNIASY ALLTYMIAHI
TGLKPGDFIH TLGDAHIYLN HIEPLKIQLQ REPRPFPKLR ILRKVEKIDD FKAEDFQIEG
YNPHPTIKME MAV
