THYX_MYCBO
ID THYX_MYCBO Reviewed; 250 AA.
AC P66931; A0A1R3Y221; O33296; X2BLF4;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 88.
DE RecName: Full=Flavin-dependent thymidylate synthase {ECO:0000255|HAMAP-Rule:MF_01408};
DE Short=FDTS {ECO:0000255|HAMAP-Rule:MF_01408};
DE EC=2.1.1.148 {ECO:0000255|HAMAP-Rule:MF_01408};
DE AltName: Full=FAD-dependent thymidylate synthase {ECO:0000255|HAMAP-Rule:MF_01408};
DE AltName: Full=Thymidylate synthase ThyX {ECO:0000255|HAMAP-Rule:MF_01408};
DE Short=TS {ECO:0000255|HAMAP-Rule:MF_01408};
DE Short=TSase {ECO:0000255|HAMAP-Rule:MF_01408};
GN Name=thyX {ECO:0000255|HAMAP-Rule:MF_01408};
GN OrderedLocusNames=BQ2027_MB2775C;
OS Mycobacterium bovis (strain ATCC BAA-935 / AF2122/97).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=233413;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-935 / AF2122/97;
RX PubMed=12788972; DOI=10.1073/pnas.1130426100;
RA Garnier T., Eiglmeier K., Camus J.-C., Medina N., Mansoor H., Pryor M.,
RA Duthoy S., Grondin S., Lacroix C., Monsempe C., Simon S., Harris B.,
RA Atkin R., Doggett J., Mayes R., Keating L., Wheeler P.R., Parkhill J.,
RA Barrell B.G., Cole S.T., Gordon S.V., Hewinson R.G.;
RT "The complete genome sequence of Mycobacterium bovis.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:7877-7882(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=ATCC BAA-935 / AF2122/97;
RX PubMed=28385856; DOI=10.1128/genomea.00157-17;
RA Malone K.M., Farrell D., Stuber T.P., Schubert O.T., Aebersold R.,
RA Robbe-Austerman S., Gordon S.V.;
RT "Updated reference genome sequence and annotation of Mycobacterium bovis
RT AF2122/97.";
RL Genome Announc. 5:E00157-E00157(2017).
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,
CC and NADPH and FADH(2) as the reductant. {ECO:0000255|HAMAP-
CC Rule:MF_01408}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + dUMP + H(+) +
CC NADPH = (6S)-5,6,7,8-tetrahydrofolate + dTMP + NADP(+);
CC Xref=Rhea:RHEA:29043, ChEBI:CHEBI:15378, ChEBI:CHEBI:15636,
CC ChEBI:CHEBI:57453, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:63528, ChEBI:CHEBI:246422; EC=2.1.1.148;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01408};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01408};
CC Note=Binds 4 FAD per tetramer. Each FAD binding site is formed by three
CC monomers. {ECO:0000255|HAMAP-Rule:MF_01408};
CC -!- PATHWAY: Pyrimidine metabolism; dTTP biosynthesis. {ECO:0000255|HAMAP-
CC Rule:MF_01408}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000255|HAMAP-Rule:MF_01408}.
CC -!- SIMILARITY: Belongs to the thymidylate synthase ThyX family.
CC {ECO:0000255|HAMAP-Rule:MF_01408}.
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DR EMBL; LT708304; SIU01393.1; -; Genomic_DNA.
DR RefSeq; NP_856421.1; NC_002945.3.
DR RefSeq; WP_003899465.1; NC_002945.4.
DR AlphaFoldDB; P66931; -.
DR SMR; P66931; -.
DR EnsemblBacteria; SIU01393; SIU01393; BQ2027_MB2775C.
DR PATRIC; fig|233413.5.peg.3041; -.
DR OMA; AKLGPRC; -.
DR UniPathway; UPA00575; -.
DR Proteomes; UP000001419; Chromosome.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0050797; F:thymidylate synthase (FAD) activity; IEA:UniProtKB-UniRule.
DR GO; GO:0006231; P:dTMP biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0006235; P:dTTP biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR Gene3D; 3.30.1360.170; -; 1.
DR HAMAP; MF_01408; ThyX; 1.
DR InterPro; IPR003669; Thymidylate_synthase_ThyX.
DR InterPro; IPR036098; Thymidylate_synthase_ThyX_sf.
DR PANTHER; PTHR34934; PTHR34934; 1.
DR Pfam; PF02511; Thy1; 1.
DR SUPFAM; SSF69796; SSF69796; 1.
DR TIGRFAMs; TIGR02170; thyX; 1.
DR PROSITE; PS51331; THYX; 1.
PE 3: Inferred from homology;
KW FAD; Flavoprotein; Methyltransferase; NADP; Nucleotide biosynthesis;
KW Transferase.
FT CHAIN 1..250
FT /note="Flavin-dependent thymidylate synthase"
FT /id="PRO_0000175571"
FT DOMAIN 7..233
FT /note="ThyX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00661"
FT MOTIF 95..105
FT /note="ThyX motif"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01408"
FT ACT_SITE 199
FT /note="Involved in ionization of N3 of dUMP, leading to its
FT activation"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01408"
FT BINDING 71
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between neighboring subunits"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01408"
FT BINDING 92..95
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01408"
FT BINDING 95..97
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between neighboring subunits"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01408"
FT BINDING 103..107
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_01408"
FT BINDING 103
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between neighboring subunits"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01408"
FT BINDING 172
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_01408"
FT BINDING 188..190
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between neighboring subunits"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01408"
FT BINDING 194
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between neighboring subunits"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01408"
FT BINDING 199
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01408"
SQ SEQUENCE 250 AA; 27591 MW; 7BACFA59B5DA7294 CRC64;
MAETAPLRVQ LIAKTDFLAP PDVPWTTDAD GGPALVEFAG RACYQSWSKP NPKTATNAGY
LRHIIDVGHF SVLEHASVSF YITGISRSCT HELIRHRHFS YSQLSQRYVP EKDSRVVVPP
GMEDDADLRH ILTEAADAAR ATYSELLAKL EAKFADQPNA ILRRKQARQA ARAVLPNATE
TRIVVTGNYR AWRHFIAMRA SEHADVEIRR LAIECLRQLA AVAPAVFADF EVTTLADGTE
VATSPLATEA
