ID   TYSY2_BACSU             Reviewed;         264 AA.
AC   P11044;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1989, sequence version 1.
DT   27-MAR-2024, entry version 157.
DE   RecName: Full=Thymidylate synthase 2 {ECO:0000255|HAMAP-Rule:MF_00008};
DE            Short=TS 2 {ECO:0000255|HAMAP-Rule:MF_00008};
DE            Short=TSase 2 {ECO:0000255|HAMAP-Rule:MF_00008};
DE            EC=2.1.1.45 {ECO:0000255|HAMAP-Rule:MF_00008};
DE   AltName: Full=Thymidylate synthase A {ECO:0000303|PubMed:2840350};
DE            Short=TS A {ECO:0000303|PubMed:2840350};
DE            Short=TSase A {ECO:0000303|PubMed:2840350};
GN   Name=thyA2 {ECO:0000255|HAMAP-Rule:MF_00008}; Synonyms=thyB;
GN   OrderedLocusNames=BSU21820;
OS   Bacillus subtilis (strain 168).
OC   Bacteria; Bacillota; Bacilli; Bacillales; Bacillaceae; Bacillus.
OX   NCBI_TaxID=224308;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=168;
RX   PubMed=2840350; DOI=10.1016/0378-1119(88)90476-3;
RA   Iwakura M., Kawata M., Tsuda K., Tanaka T.;
RT   "Nucleotide sequence of the thymidylate synthase B and dihydrofolate
RT   reductase genes contained in one Bacillus subtilis operon.";
RL   Gene 64:9-20(1988).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=168 / Marburg / ATCC 6051 / DSM 10 / JCM 1465 / NBRC 13719 /
RC   NCIMB 3610 / NRRL NRS-744 / VKM B-501;
RX   PubMed=8969496; DOI=10.1099/13500872-142-11-3005;
RA   Capuano V., Galleron N., Pujic P., Sorokin A., Ehrlich S.D.;
RT   "Organization of the Bacillus subtilis 168 chromosome between kdg and the
RT   attachment site of the SP beta prophage: use of long accurate PCR and yeast
RT   artificial chromosomes for sequencing.";
RL   Microbiology 142:3005-3015(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=168, and ATCC 6633 / PCI 219 / NRS 231;
RX   PubMed=8510640; DOI=10.1007/bf00281594;
RA   Montorsi M., Lorenzetti R.;
RT   "Heat-stable and heat-labile thymidylate synthases B of Bacillus subtilis:
RT   comparison of the nucleotide and amino acid sequences.";
RL   Mol. Gen. Genet. 239:1-5(1993).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=168;
RX   PubMed=9384377; DOI=10.1038/36786;
RA   Kunst F., Ogasawara N., Moszer I., Albertini A.M., Alloni G., Azevedo V.,
RA   Bertero M.G., Bessieres P., Bolotin A., Borchert S., Borriss R.,
RA   Boursier L., Brans A., Braun M., Brignell S.C., Bron S., Brouillet S.,
RA   Bruschi C.V., Caldwell B., Capuano V., Carter N.M., Choi S.-K.,
RA   Codani J.-J., Connerton I.F., Cummings N.J., Daniel R.A., Denizot F.,
RA   Devine K.M., Duesterhoeft A., Ehrlich S.D., Emmerson P.T., Entian K.-D.,
RA   Errington J., Fabret C., Ferrari E., Foulger D., Fritz C., Fujita M.,
RA   Fujita Y., Fuma S., Galizzi A., Galleron N., Ghim S.-Y., Glaser P.,
RA   Goffeau A., Golightly E.J., Grandi G., Guiseppi G., Guy B.J., Haga K.,
RA   Haiech J., Harwood C.R., Henaut A., Hilbert H., Holsappel S., Hosono S.,
RA   Hullo M.-F., Itaya M., Jones L.-M., Joris B., Karamata D., Kasahara Y.,
RA   Klaerr-Blanchard M., Klein C., Kobayashi Y., Koetter P., Koningstein G.,
RA   Krogh S., Kumano M., Kurita K., Lapidus A., Lardinois S., Lauber J.,
RA   Lazarevic V., Lee S.-M., Levine A., Liu H., Masuda S., Mauel C.,
RA   Medigue C., Medina N., Mellado R.P., Mizuno M., Moestl D., Nakai S.,
RA   Noback M., Noone D., O'Reilly M., Ogawa K., Ogiwara A., Oudega B.,
RA   Park S.-H., Parro V., Pohl T.M., Portetelle D., Porwollik S.,
RA   Prescott A.M., Presecan E., Pujic P., Purnelle B., Rapoport G., Rey M.,
RA   Reynolds S., Rieger M., Rivolta C., Rocha E., Roche B., Rose M., Sadaie Y.,
RA   Sato T., Scanlan E., Schleich S., Schroeter R., Scoffone F., Sekiguchi J.,
RA   Sekowska A., Seror S.J., Serror P., Shin B.-S., Soldo B., Sorokin A.,
RA   Tacconi E., Takagi T., Takahashi H., Takemaru K., Takeuchi M.,
RA   Tamakoshi A., Tanaka T., Terpstra P., Tognoni A., Tosato V., Uchiyama S.,
RA   Vandenbol M., Vannier F., Vassarotti A., Viari A., Wambutt R., Wedler E.,
RA   Wedler H., Weitzenegger T., Winters P., Wipat A., Yamamoto H., Yamane K.,
RA   Yasumoto K., Yata K., Yoshida K., Yoshikawa H.-F., Zumstein E.,
RA   Yoshikawa H., Danchin A.;
RT   "The complete genome sequence of the Gram-positive bacterium Bacillus
RT   subtilis.";
RL   Nature 390:249-256(1997).
CC   -!- FUNCTION: Catalyzes the reductive methylation of 2'-deoxyuridine-5'-
CC       monophosphate (dUMP) to 2'-deoxythymidine-5'-monophosphate (dTMP) while
CC       utilizing 5,10-methylenetetrahydrofolate (mTHF) as the methyl donor and
CC       reductant in the reaction, yielding dihydrofolate (DHF) as a by-
CC       product. This enzymatic reaction provides an intracellular de novo
CC       source of dTMP, an essential precursor for DNA biosynthesis.
CC       {ECO:0000255|HAMAP-Rule:MF_00008}.
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:0000255|HAMAP-Rule:MF_00008};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Temperature dependence:
CC         Thermolabile. Inactive at 46 degrees Celsius.;
CC   -!- PATHWAY: Pyrimidine metabolism; dTTP biosynthesis. {ECO:0000255|HAMAP-
CC       Rule:MF_00008}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_00008}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00008}.
CC   -!- MISCELLANEOUS: B.subtilis strain 168 possesses two thymidylate
CC       synthases, a major form ThyA and a minor form ThyB.
CC   -!- SIMILARITY: Belongs to the thymidylate synthase family. Bacterial-type
CC       ThyA subfamily. {ECO:0000255|HAMAP-Rule:MF_00008}.
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DR   EMBL; X69661; CAA49350.1; -; Genomic_DNA.
DR   EMBL; L77246; AAA96634.1; -; Genomic_DNA.
DR   EMBL; M20012; AAA22852.1; -; Genomic_DNA.
DR   EMBL; AL009126; CAB14100.1; -; Genomic_DNA.
DR   PIR; JT0290; SYBSTB.
DR   PIR; S35239; S35239.
DR   RefSeq; NP_390065.1; NC_000964.3.
DR   RefSeq; WP_004398587.1; NZ_JNCM01000036.1.
DR   AlphaFoldDB; P11044; -.
DR   SMR; P11044; -.
DR   IntAct; P11044; 6.
DR   STRING; 224308.BSU21820; -.
DR   PaxDb; 224308-BSU21820; -.
DR   EnsemblBacteria; CAB14100; CAB14100; BSU_21820.
DR   GeneID; 939092; -.
DR   KEGG; bsu:BSU21820; -.
DR   PATRIC; fig|224308.179.peg.2384; -.
DR   eggNOG; COG0207; Bacteria.
DR   InParanoid; P11044; -.
DR   OrthoDB; 9774633at2; -.
DR   PhylomeDB; P11044; -.
DR   BioCyc; BSUB:BSU21820-MONOMER; -.
DR   SABIO-RK; P11044; -.
DR   UniPathway; UPA00575; -.
DR   Proteomes; UP000001570; Chromosome.
DR   GO; GO:0005829; C:cytosol; 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; 2.
DR   PANTHER; PTHR11548:SF9; 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.
PE   1: Evidence at protein level;
KW   Cytoplasm; Methyltransferase; Nucleotide biosynthesis; Reference proteome;
KW   Transferase.
FT   CHAIN           1..264
FT                   /note="Thymidylate synthase 2"
FT                   /id="PRO_0000140932"
FT   ACT_SITE        146
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00008"
FT   BINDING         21
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:0000255|HAMAP-Rule:MF_00008"
FT   BINDING         51
FT                   /ligand="(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate"
FT                   /ligand_id="ChEBI:CHEBI:15636"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00008"
FT   BINDING         126..127
FT                   /ligand="dUMP"
FT                   /ligand_id="ChEBI:CHEBI:246422"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00008"
FT   BINDING         166..169
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:0000255|HAMAP-Rule:MF_00008"
FT   BINDING         169
FT                   /ligand="(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate"
FT                   /ligand_id="ChEBI:CHEBI:15636"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00008"
FT   BINDING         177
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:0000255|HAMAP-Rule:MF_00008"
FT   BINDING         207..209
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:0000255|HAMAP-Rule:MF_00008"
FT   BINDING         263
FT                   /ligand="(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate"
FT                   /ligand_id="ChEBI:CHEBI:15636"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00008"
FT   VARIANT         7
FT                   /note="F -> L (in strain: ATCC 6633)"
FT   VARIANT         37
FT                   /note="N -> H (in strain: ATCC 6633)"
FT   VARIANT         39
FT                   /note="R -> Q (in strain: ATCC 6633)"
FT   VARIANT         187
FT                   /note="I -> M (in strain: ATCC 6633)"
FT   VARIANT         221
FT                   /note="E -> T (in strain: ATCC 6633)"
FT   VARIANT         224
FT                   /note="V -> L (in strain: ATCC 6633)"
FT   VARIANT         229
FT                   /note="Q -> K (in strain: ATCC 6633)"
FT   VARIANT         235..236
FT                   /note="KV -> EI (in strain: ATCC 6633)"
SQ   SEQUENCE   264 AA;  30538 MW;  1BFE1F1BD8202E64 CRC64;
     MKQYKDFCRH VLEHGEKKGD RTGTGTISTF GYQMRFNLRE GFPMLTTKKL HFKSIAHELL
     WFLKGDTNVR YLQENGVRIW NEWADENGEL GPVYGSQWRS WRGADGETID QISRLIEDIK
     TNPNSRRLIV SAWNVGEIDK MALPPCHCLF QFYVSDGKLS CQLYQRSADV FLGVPFNIAS
     YALLTMIIAH VTGLEPGEFI HTFGDVHIYQ NHIEQVNLQL ERDVRPLPQL RFARKVDSIF
     NFAFEDFIIE DYDPHPHIKG AVSV
//