ID THYX_RICFE Reviewed; 294 AA. AC Q4UM78; DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2005, sequence version 1. DT 27-MAR-2024, 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=RF_0491; OS Rickettsia felis (strain ATCC VR-1525 / URRWXCal2) (Rickettsia azadi). OC Bacteria; Pseudomonadota; Alphaproteobacteria; Rickettsiales; OC Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group. OX NCBI_TaxID=315456; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC VR-1525 / URRWXCal2; RX PubMed=15984913; DOI=10.1371/journal.pbio.0030248; RA Ogata H., Renesto P., Audic S., Robert C., Blanc G., Fournier P.-E., RA Parinello H., Claverie J.-M., Raoult D.; RT "The genome sequence of Rickettsia felis identifies the first putative RT conjugative plasmid in an obligate intracellular parasite."; RL PLoS Biol. 3:1-12(2005). 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; Evidence={ECO:0000255|HAMAP- CC 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; CP000053; AAY61342.1; -; Genomic_DNA. DR AlphaFoldDB; Q4UM78; -. DR SMR; Q4UM78; -. DR STRING; 315456.RF_0491; -. DR KEGG; rfe:RF_0491; -. DR eggNOG; COG1351; Bacteria. DR HOGENOM; CLU_067790_0_0_5; -. DR OrthoDB; 9774464at2; -. DR UniPathway; UPA00575; -. DR Proteomes; UP000008548; 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 CDD; cd20175; ThyX; 1. 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 NCBIfam; TIGR02170; thyX; 1. DR PANTHER; PTHR34934; FLAVIN-DEPENDENT THYMIDYLATE SYNTHASE; 1. DR PANTHER; PTHR34934:SF1; FLAVIN-DEPENDENT THYMIDYLATE SYNTHASE; 1. DR Pfam; PF02511; Thy1; 1. DR SUPFAM; SSF69796; Thymidylate synthase-complementing protein Thy1; 1. DR PROSITE; PS51331; THYX; 1. PE 3: Inferred from homology; KW FAD; Flavoprotein; Methyltransferase; NADP; Nucleotide biosynthesis; KW Transferase. FT CHAIN 1..294 FT /note="Flavin-dependent thymidylate synthase" FT /id="PRO_0000272379" FT DOMAIN 27..250 FT /note="ThyX" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00661" FT MOTIF 96..106 FT /note="ThyX motif" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01408" FT ACT_SITE 216 FT /note="Involved in ionization of N3 of dUMP, leading to its FT activation" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01408" FT BINDING 73 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 93..96 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 96..98 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 104..108 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 104 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 189 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 205..207 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 211 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 216 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 294 AA; 34308 MW; BFB8A315D6394E04 CRC64; MHNTTKRVTV PALEEILYEP IKVLDHGFIR VIDYMGDDSA IVQAARVSYG KGTKQLNQDK GLINYLLRHY HTTPFEMCDI KFHIKLPIFI ARQWIRHRTA SVNEYSARYS ILGNEFYLPE PANIASQSAV NKQCREGDSL PKEGAEKVLA ILEEDAKQCY GHYKELMNAD EDGNIIDENN TGIARELARM NLTLNYYTEW YWKINLHNLL HFLRLRADPH AQYEIRVYAE KMLEIVKAWV PFTYEAFEEY RLQGANISRK GLDVIKRMIK GEKVTHESSG MTKREWEELM KIFG //