ID   TYSY_METTM              Reviewed;         223 AA.
AC   P80305; D9PX15;
DT   01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   25-MAY-2022, entry version 117.
DE   RecName: Full=Putative thymidylate synthase;
DE            Short=TS;
DE            Short=TSase;
DE            EC=2.1.1.-;
GN   Name=thyA; OrderedLocusNames=MTBMA_c11700;
OS   Methanothermobacter marburgensis (strain ATCC BAA-927 / DSM 2133 / JCM
OS   14651 / NBRC 100331 / OCM 82 / Marburg) (Methanobacterium
OS   thermoautotrophicum).
OC   Archaea; Euryarchaeota; Methanomada group; Methanobacteria;
OC   Methanobacteriales; Methanobacteriaceae; Methanothermobacter.
OX   NCBI_TaxID=79929;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC BAA-927 / DSM 2133 / JCM 14651 / NBRC 100331 / OCM 82 /
RC   Marburg;
RX   PubMed=8617278; DOI=10.1111/j.1432-1033.1996.00294.x;
RA   Vaupel M., Dietz H., Linder D., Thauer R.K.;
RT   "Primary structure of cyclohydrolase (Mch) from Methanobacterium
RT   thermoautotrophicum (strain Marburg) and functional expression of the mch
RT   gene in Escherichia coli.";
RL   Eur. J. Biochem. 236:294-300(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC BAA-927 / DSM 2133 / JCM 14651 / NBRC 100331 / OCM 82 /
RC   Marburg;
RX   PubMed=20802048; DOI=10.1128/jb.00844-10;
RA   Liesegang H., Kaster A.K., Wiezer A., Goenrich M., Wollherr A., Seedorf H.,
RA   Gottschalk G., Thauer R.K.;
RT   "Complete genome sequence of Methanothermobacter marburgensis, a
RT   methanoarchaeon model organism.";
RL   J. Bacteriol. 192:5850-5851(2010).
RN   [3]
RP   PROTEIN SEQUENCE OF 2-30, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP   SUBUNIT.
RC   STRAIN=ATCC BAA-927 / DSM 2133 / JCM 14651 / NBRC 100331 / OCM 82 /
RC   Marburg;
RX   PubMed=8143733; DOI=10.1111/j.1432-1033.1994.tb18680.x;
RA   Krone U.E., McFarlan S.C., Hogenkamp H.P.C.;
RT   "Purification and partial characterization of a putative thymidylate
RT   synthase from Methanobacterium thermoautotrophicum.";
RL   Eur. J. Biochem. 220:789-794(1994).
CC   -!- FUNCTION: May catalyze the biosynthesis of dTMP using an unknown
CC       cosubstrate. In vitro, also catalyzes the dehalogenation of 5-bromo-
CC       deoxyuridine monophosphate (Br-dUMP) and the tritium exchange of [5-
CC       3H]deoxyuridine monophosphate ([5-3H]dUMP).
CC       {ECO:0000269|PubMed:8143733}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=7 uM for [5-3H]dUMP {ECO:0000269|PubMed:8143733};
CC         KM=14 uM for Br-dUMP {ECO:0000269|PubMed:8143733};
CC       pH dependence:
CC         Optimum pH is 9.0 with [5-3H]dUMP as substrate, and 7.0 with Br-dUMP
CC         as substrate. {ECO:0000269|PubMed:8143733};
CC       Temperature dependence:
CC         Optimum temperature is 70 degrees Celsius with [5-3H]dUMP as
CC         substrate, and 50-70 degrees Celsius with Br-dUMP as substrate.
CC         Heating the protein for 10 min at 100 degrees Celsius abolished the
CC         activity. {ECO:0000269|PubMed:8143733};
CC   -!- PATHWAY: Pyrimidine metabolism; dTTP biosynthesis.
CC   -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:8143733}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the thymidylate synthase family. Archaeal-type
CC       ThyA subfamily. {ECO:0000305}.
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DR   EMBL; X92082; CAA63063.1; -; Genomic_DNA.
DR   EMBL; CP001710; ADL58763.1; -; Genomic_DNA.
DR   RefSeq; WP_013295985.1; NC_014408.1.
DR   AlphaFoldDB; P80305; -.
DR   SMR; P80305; -.
DR   STRING; 79929.MTBMA_c11700; -.
DR   EnsemblBacteria; ADL58763; ADL58763; MTBMA_c11700.
DR   GeneID; 9704878; -.
DR   KEGG; mmg:MTBMA_c11700; -.
DR   PATRIC; fig|79929.8.peg.1139; -.
DR   HOGENOM; CLU_084975_0_0_2; -.
DR   OMA; HHSVSMH; -.
DR   OrthoDB; 57461at2157; -.
DR   UniPathway; UPA00575; -.
DR   Proteomes; UP000000345; Chromosome.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0004799; F:thymidylate synthase 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; cd00351; TS_Pyrimidine_HMase; 1.
DR   Gene3D; 3.30.572.10; -; 1.
DR   HAMAP; MF_01686; Thymidy_synth_arch; 1.
DR   InterPro; IPR045097; Thymidate_synth/dCMP_Mease.
DR   InterPro; IPR023451; Thymidate_synth/dCMP_Mease_dom.
DR   InterPro; IPR036926; Thymidate_synth/dCMP_Mease_sf.
DR   InterPro; IPR014620; Thymidylate_synthase_arc.
DR   InterPro; IPR020940; Thymidylate_synthase_AS.
DR   PANTHER; PTHR11548; PTHR11548; 1.
DR   Pfam; PF00303; Thymidylat_synt; 1.
DR   PIRSF; PIRSF036752; TSase_MJ051; 1.
DR   SUPFAM; SSF55831; SSF55831; 1.
DR   TIGRFAMs; TIGR03283; thy_syn_methano; 1.
DR   PROSITE; PS00091; THYMIDYLATE_SYNTHASE; 1.
PE   1: Evidence at protein level;
KW   Cytoplasm; Direct protein sequencing; Methyltransferase;
KW   Nucleotide biosynthesis; Transferase.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|PubMed:8143733"
FT   CHAIN           2..223
FT                   /note="Putative thymidylate synthase"
FT                   /id="PRO_0000141059"
FT   ACT_SITE        146
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   223 AA;  25589 MW;  A4C148197E5344C5 CRC64;
     MAYEISVDEI AEGWLKLVEK IMSDGREIRD ERGSLTREVM NTVVTIKNPL GRSGDFYHLP
     ARSLINIRVP EGYFWSGEKL EKYSEQFLSD DRKGFVYTYG NRLRAHFGVD QVDRAIERLK
     NCKESRRATM VTWDPKIDTE SDEVPCMILV DFKVREGRLF TTALWRSHDI YGAWFPNAVG
     LAYLADHVAS EVGVEVGHIT IHSISAHIYE VNFKEAKEVI KNG