THYX_AQUAE
ID THYX_AQUAE Reviewed; 317 AA.
AC O66883;
DT 11-JUL-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=Flavin-dependent thymidylate synthase {ECO:0000250|UniProtKB:Q9WYT0};
DE Short=FDTS {ECO:0000250|UniProtKB:Q9WYT0};
DE EC=2.1.1.148 {ECO:0000250|UniProtKB:Q9WYT0};
DE AltName: Full=FAD-dependent thymidylate synthase {ECO:0000250|UniProtKB:Q9WYT0};
DE AltName: Full=Thymidylate synthase ThyX {ECO:0000250|UniProtKB:Q9WYT0};
DE Short=TS {ECO:0000250|UniProtKB:Q9WYT0};
DE Short=TSase {ECO:0000250|UniProtKB:Q9WYT0};
GN Name=thyX {ECO:0000250|UniProtKB:Q9WYT0}; OrderedLocusNames=aq_640;
OS Aquifex aeolicus (strain VF5).
OC Bacteria; Aquificae; Aquificales; Aquificaceae; Aquifex.
OX NCBI_TaxID=224324;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=VF5;
RX PubMed=9537320; DOI=10.1038/32831;
RA Deckert G., Warren P.V., Gaasterland T., Young W.G., Lenox A.L.,
RA Graham D.E., Overbeek R., Snead M.A., Keller M., Aujay M., Huber R.,
RA Feldman R.A., Short J.M., Olsen G.J., Swanson R.V.;
RT "The complete genome of the hyperthermophilic bacterium Aquifex aeolicus.";
RL Nature 392:353-358(1998).
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:0000250|UniProtKB:Q9WYT0}.
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:0000250|UniProtKB:Q9WYT0};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:Q9WYT0};
CC Note=Binds 4 FAD per tetramer. Each FAD binding site is formed by three
CC monomers. {ECO:0000250|UniProtKB:Q9WYT0};
CC -!- PATHWAY: Pyrimidine metabolism; dTTP biosynthesis.
CC {ECO:0000250|UniProtKB:Q9WYT0}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:Q9WYT0}.
CC -!- SIMILARITY: Belongs to the thymidylate synthase ThyX family.
CC {ECO:0000305}.
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DR EMBL; AE000657; AAC06847.1; -; Genomic_DNA.
DR PIR; G70356; G70356.
DR RefSeq; NP_213443.1; NC_000918.1.
DR AlphaFoldDB; O66883; -.
DR STRING; 224324.aq_640; -.
DR EnsemblBacteria; AAC06847; AAC06847; aq_640.
DR KEGG; aae:aq_640; -.
DR PATRIC; fig|224324.8.peg.522; -.
DR eggNOG; COG1351; Bacteria.
DR HOGENOM; CLU_828483_0_0_0; -.
DR InParanoid; O66883; -.
DR OMA; HASPFEH; -.
DR OrthoDB; 896350at2; -.
DR UniPathway; UPA00575; -.
DR Proteomes; UP000000798; Chromosome.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IBA:GO_Central.
DR GO; GO:0070402; F:NADPH binding; IBA:GO_Central.
DR GO; GO:0050797; F:thymidylate synthase (FAD) activity; 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 Gene3D; 3.30.1360.170; -; 2.
DR InterPro; IPR003669; Thymidylate_synthase_ThyX.
DR InterPro; IPR036098; Thymidylate_synthase_ThyX_sf.
DR PANTHER; PTHR34934; PTHR34934; 1.
DR Pfam; PF02511; Thy1; 2.
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 Reference proteome; Transferase.
FT CHAIN 1..317
FT /note="Flavin-dependent thymidylate synthase"
FT /id="PRO_0000175552"
FT DOMAIN 100..317
FT /note="ThyX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00661"
FT REGION 55..166
FT /note="Insert"
FT MOTIF 181..191
FT /note="ThyX motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00661"
FT ACT_SITE 286
FT /note="Involved in ionization of N3 of dUMP, leading to its
FT activation"
FT /evidence="ECO:0000250|UniProtKB:Q9WYT0"
FT BINDING 46
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between neighboring subunits"
FT /evidence="ECO:0000250|UniProtKB:Q9WYT0"
FT BINDING 178..181
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:Q9WYT0"
FT BINDING 181..183
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between neighboring subunits"
FT /evidence="ECO:0000250|UniProtKB:Q9WYT0"
FT BINDING 189..193
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:0000250|UniProtKB:Q9WYT0"
FT BINDING 189
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between neighboring subunits"
FT /evidence="ECO:0000250|UniProtKB:Q9WYT0"
FT BINDING 259
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:0000250|UniProtKB:Q9WYT0"
FT BINDING 281
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between neighboring subunits"
FT /evidence="ECO:0000250|UniProtKB:Q9WYT0"
FT BINDING 286
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:Q9WYT0"
SQ SEQUENCE 317 AA; 37642 MW; 290CDDD48D3AF9B9 CRC64;
MMKIYLMGSD QRIVRCARVS FAKDSYVDEK RDKRLIRYLF KHRHASPFEH NIIAFEWKKE
KWIELLSKLE NPTVQVYYSN GFVFLNLRNA INVWELLPDA VKERIKEAFP TTYGVIQRRG
EIEDEELYSL PYTKDKAYVK EKIETSSGWI GLVDKLELET DMDFYTFVVE CPLFVARQWM
RHRFGSYNEV SKRYVGKEFL EFYLPKYIRK QAEKNKQASV DEPISESEVF IKKIENLISK
SVKLYEEIIE KGGAKELARG VLPQFMKTRF YWTVPRISLD NFITLRTHEG AQKEIREFAE
AIKEMVGYRG TDKKNVI
