THYX_EHRRG
ID THYX_EHRRG Reviewed; 297 AA.
AC Q5FG35;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 92.
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=ERGA_CDS_07060;
OS Ehrlichia ruminantium (strain Gardel).
OC Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales;
OC Anaplasmataceae; Ehrlichia.
OX NCBI_TaxID=302409;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Gardel;
RX PubMed=16547041; DOI=10.1128/jb.188.7.2533-2542.2006;
RA Frutos R., Viari A., Ferraz C., Morgat A., Eychenie S., Kandassamy Y.,
RA Chantal I., Bensaid A., Coissac E., Vachiery N., Demaille J., Martinez D.;
RT "Comparative genomic analysis of three strains of Ehrlichia ruminantium
RT reveals an active process of genome size plasticity.";
RL J. Bacteriol. 188:2533-2542(2006).
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; CR925677; CAI28158.1; -; Genomic_DNA.
DR AlphaFoldDB; Q5FG35; -.
DR SMR; Q5FG35; -.
DR EnsemblBacteria; CAI28158; CAI28158; ERGA_CDS_07060.
DR KEGG; erg:ERGA_CDS_07060; -.
DR HOGENOM; CLU_067790_0_0_5; -.
DR OMA; EWARLMP; -.
DR UniPathway; UPA00575; -.
DR Proteomes; UP000000533; 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..297
FT /note="Flavin-dependent thymidylate synthase"
FT /id="PRO_0000175562"
FT DOMAIN 41..251
FT /note="ThyX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00661"
FT MOTIF 110..120
FT /note="ThyX motif"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01408"
FT ACT_SITE 217
FT /note="Involved in ionization of N3 of dUMP, leading to its
FT activation"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01408"
FT BINDING 87
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 107..110
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 110..112
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 118..122
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 118
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 190
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 206..208
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 212
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 217
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 297 AA; 34762 MW; 81872D17504492F7 CRC64;
MLVLSIRIKV WQTMESEITK RIVVPELEDI LYKEHKVLDK GFVRLVDYMG SDESVVQAAR
ISYGRGTKSV SQDAALINYL MRHSHTTPFE MCEIKFHIKL PIFVARQWVR HRTANVNEYS
ARYSVLDHEF YIPELDHVAT QSEDNAQGRG NSLSNEDAQY VTDLLKRDSD MVYETYNKFL
IKGVSREISR ISLTLNYYTE WYWKIDLHNL LHFLRLRSDV HAQYEIRVYA ETMLEIVKKW
VPLTYAAFVE YCLESQSFSK SALSVVKKLI AGEDVAREDT GIGKREWREL MDVLADK
