ID A0A286E1A9_9ACTN Unreviewed; 240 AA.
AC A0A286E1A9;
DT 22-NOV-2017, integrated into UniProtKB/TrEMBL.
DT 22-NOV-2017, sequence version 1.
DT 24-JAN-2024, entry version 26.
DE RecName: Full=Flavin-dependent thymidylate synthase {ECO:0000256|HAMAP-Rule:MF_01408};
DE Short=FDTS {ECO:0000256|HAMAP-Rule:MF_01408};
DE EC=2.1.1.148 {ECO:0000256|HAMAP-Rule:MF_01408};
DE AltName: Full=FAD-dependent thymidylate synthase {ECO:0000256|HAMAP-Rule:MF_01408};
DE AltName: Full=Thymidylate synthase ThyX {ECO:0000256|HAMAP-Rule:MF_01408};
DE Short=TS {ECO:0000256|HAMAP-Rule:MF_01408};
DE Short=TSase {ECO:0000256|HAMAP-Rule:MF_01408};
GN Name=thyX {ECO:0000256|HAMAP-Rule:MF_01408};
GN ORFNames=SAMN06297387_118126 {ECO:0000313|EMBL:SOD64673.1};
OS Streptomyces zhaozhouensis.
OC Bacteria; Actinomycetota; Actinomycetes; Kitasatosporales;
OC Streptomycetaceae; Streptomyces.
OX NCBI_TaxID=1300267 {ECO:0000313|EMBL:SOD64673.1, ECO:0000313|Proteomes:UP000219072};
RN [1] {ECO:0000313|EMBL:SOD64673.1, ECO:0000313|Proteomes:UP000219072}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CGMCC 4.7095 {ECO:0000313|EMBL:SOD64673.1,
RC ECO:0000313|Proteomes:UP000219072};
RA Ehlers B., Leendertz F.H.;
RL Submitted (SEP-2017) 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:0000256|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:0000256|HAMAP-Rule:MF_01408};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000256|HAMAP-Rule:MF_01408};
CC Note=Binds 4 FAD per tetramer. Each FAD binding site is formed by three
CC monomers. {ECO:0000256|HAMAP-Rule:MF_01408};
CC -!- PATHWAY: Pyrimidine metabolism; dTTP biosynthesis. {ECO:0000256|HAMAP-
CC Rule:MF_01408}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000256|HAMAP-Rule:MF_01408}.
CC -!- SIMILARITY: Belongs to the thymidylate synthase ThyX family.
CC {ECO:0000256|HAMAP-Rule:MF_01408}.
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DR EMBL; OCNE01000018; SOD64673.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A286E1A9; -.
DR OrthoDB; 9774464at2; -.
DR UniPathway; UPA00575; -.
DR Proteomes; UP000219072; Unassembled WGS sequence.
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 {ECO:0000256|ARBA:ARBA00022827, ECO:0000256|HAMAP-Rule:MF_01408};
KW Flavoprotein {ECO:0000256|ARBA:ARBA00022630, ECO:0000256|HAMAP-
KW Rule:MF_01408};
KW Methyltransferase {ECO:0000256|ARBA:ARBA00022603, ECO:0000256|HAMAP-
KW Rule:MF_01408};
KW NADP {ECO:0000256|ARBA:ARBA00022857, ECO:0000256|HAMAP-Rule:MF_01408};
KW Nucleotide biosynthesis {ECO:0000256|ARBA:ARBA00022727, ECO:0000256|HAMAP-
KW Rule:MF_01408}; Reference proteome {ECO:0000313|Proteomes:UP000219072};
KW Transferase {ECO:0000256|HAMAP-Rule:MF_01408}.
FT ACT_SITE 194
FT /note="Involved in ionization of N3 of dUMP, leading to its
FT activation"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01408"
FT BINDING 63
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between neighboring subunits"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01408"
FT BINDING 83..86
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01408"
FT BINDING 86..88
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between neighboring subunits"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01408"
FT BINDING 95..99
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:0000256|HAMAP-Rule:MF_01408"
FT BINDING 95
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between neighboring subunits"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01408"
FT BINDING 167
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:0000256|HAMAP-Rule:MF_01408"
FT BINDING 183..185
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between neighboring subunits"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01408"
FT BINDING 189
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between neighboring subunits"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01408"
FT BINDING 194
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01408"
SQ SEQUENCE 240 AA; 27328 MW; E94BEC24BA7D2D62 CRC64;
MTDTPRFRSD MTVELVKHSA SDTDVLFAAR VSTAGERSLE EVGRDPERSK GLINYLLRDR
HGSPFEHNSM TFLVSAPIFV FREFHRHRVG WSYNEESGRY RELAPVFYVP DERRPLVQRG
RPGKYEFVAG SAEQHALVGK VLEDSYRQSY AAYQELLEAG VAREVARASL PVALYSTMYA
TCNARSLMHF LGLRTKDERA KVPSFPQREI EMVAELMEAE WARLMPLTHA AFNANGRVAP
//
