THYX_THET8
ID THYX_THET8 Reviewed; 270 AA.
AC Q5SJB8;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 86.
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}; OrderedLocusNames=TTHA1096;
OS Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8).
OC Bacteria; Deinococcus-Thermus; Deinococci; Thermales; Thermaceae; Thermus.
OX NCBI_TaxID=300852;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 27634 / DSM 579 / HB8;
RA Masui R., Kurokawa K., Nakagawa N., Tokunaga F., Koyama Y., Shibata T.,
RA Oshima T., Yokoyama S., Yasunaga T., Kuramitsu S.;
RT "Complete genome sequence of Thermus thermophilus HB8.";
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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; AP008226; BAD70919.1; -; Genomic_DNA.
DR RefSeq; WP_011228435.1; NC_006461.1.
DR RefSeq; YP_144362.1; NC_006461.1.
DR PDB; 6J61; X-ray; 2.50 A; A/B/C/D=1-270.
DR PDBsum; 6J61; -.
DR AlphaFoldDB; Q5SJB8; -.
DR SMR; Q5SJB8; -.
DR STRING; 300852.55772478; -.
DR PRIDE; Q5SJB8; -.
DR EnsemblBacteria; BAD70919; BAD70919; BAD70919.
DR GeneID; 3168967; -.
DR KEGG; ttj:TTHA1096; -.
DR PATRIC; fig|300852.9.peg.1076; -.
DR eggNOG; COG1351; Bacteria.
DR HOGENOM; CLU_067790_0_0_0; -.
DR OMA; EWARLMP; -.
DR PhylomeDB; Q5SJB8; -.
DR BRENDA; 2.1.1.148; 2305.
DR UniPathway; UPA00575; -.
DR Proteomes; UP000000532; 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 1: Evidence at protein level;
KW 3D-structure; FAD; Flavoprotein; Methyltransferase; NADP;
KW Nucleotide biosynthesis; Reference proteome; Transferase.
FT CHAIN 1..270
FT /note="Flavin-dependent thymidylate synthase"
FT /id="PRO_0000175581"
FT DOMAIN 13..218
FT /note="ThyX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00661"
FT MOTIF 82..92
FT /note="ThyX motif"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01408"
FT ACT_SITE 184
FT /note="Involved in ionization of N3 of dUMP, leading to its
FT activation"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01408"
FT BINDING 59
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 79..82
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 82..84
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 90..94
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 90
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 157
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 173..175
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 179
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 184
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 STRAND 6..9
FT /evidence="ECO:0007829|PDB:6J61"
FT TURN 10..12
FT /evidence="ECO:0007829|PDB:6J61"
FT STRAND 13..21
FT /evidence="ECO:0007829|PDB:6J61"
FT HELIX 24..32
FT /evidence="ECO:0007829|PDB:6J61"
FT HELIX 42..54
FT /evidence="ECO:0007829|PDB:6J61"
FT HELIX 59..63
FT /evidence="ECO:0007829|PDB:6J61"
FT STRAND 65..73
FT /evidence="ECO:0007829|PDB:6J61"
FT HELIX 74..80
FT /evidence="ECO:0007829|PDB:6J61"
FT STRAND 86..90
FT /evidence="ECO:0007829|PDB:6J61"
FT TURN 93..95
FT /evidence="ECO:0007829|PDB:6J61"
FT HELIX 132..148
FT /evidence="ECO:0007829|PDB:6J61"
FT HELIX 153..156
FT /evidence="ECO:0007829|PDB:6J61"
FT HELIX 157..159
FT /evidence="ECO:0007829|PDB:6J61"
FT STRAND 164..173
FT /evidence="ECO:0007829|PDB:6J61"
FT HELIX 174..184
FT /evidence="ECO:0007829|PDB:6J61"
FT HELIX 191..207
FT /evidence="ECO:0007829|PDB:6J61"
FT HELIX 209..218
FT /evidence="ECO:0007829|PDB:6J61"
FT TURN 219..221
FT /evidence="ECO:0007829|PDB:6J61"
FT STRAND 223..225
FT /evidence="ECO:0007829|PDB:6J61"
FT HELIX 227..236
FT /evidence="ECO:0007829|PDB:6J61"
FT HELIX 239..248
FT /evidence="ECO:0007829|PDB:6J61"
FT HELIX 253..263
FT /evidence="ECO:0007829|PDB:6J61"
SQ SEQUENCE 270 AA; 31006 MW; 5FED30A827E39907 CRC64;
MEGPLTIPVL DKGFVRLVDQ MGDDRAIVQA ARVSYGEGTK TVREDAALID YLMRHRHTSP
FEMVVFKFHV KAPIFVARQW FRHRTASVNE ISGRYSILKE EFYEPEAFRK QAKRNKQASE
GALLDEEALA LLRKVQQEAY GAYRALLEKG VAREMARMVL PLNLYTEFYW KQDLHNLFHF
LKLRLAPEAQ WEIRQYARAI AEIVKERVPL AWAAFEEHLL EGAFLSRTEL RALRGLLTPE
VYEKALSSLG LGGSRLKEAL EKVFGPGEAL
