TYSY2_BACSU
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 03-AUG-2022, entry version 150.
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; Firmicutes; 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 / NCIMB
RC 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; P11044; -.
DR PRIDE; P11044; -.
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 OMA; KQYLDLC; -.
DR PhylomeDB; P11044; -.
DR BioCyc; BSUB:BSU21820-MON; -.
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; -; 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; 2.
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
