ID D0N806_PHYIT Unreviewed; 509 AA.
AC D0N806;
DT 15-DEC-2009, integrated into UniProtKB/TrEMBL.
DT 15-DEC-2009, sequence version 1.
DT 24-JAN-2024, entry version 78.
DE RecName: Full=Bifunctional dihydrofolate reductase-thymidylate synthase {ECO:0000256|ARBA:ARBA00019798, ECO:0000256|PIRNR:PIRNR000389};
GN ORFNames=PITG_06749 {ECO:0000313|EMBL:EEY53123.1};
OS Phytophthora infestans (strain T30-4) (Potato late blight agent).
OC Eukaryota; Sar; Stramenopiles; Oomycota; Peronosporales; Peronosporaceae;
OC Phytophthora.
OX NCBI_TaxID=403677 {ECO:0000313|EMBL:EEY53123.1, ECO:0000313|Proteomes:UP000006643};
RN [1] {ECO:0000313|Proteomes:UP000006643}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=T30-4 {ECO:0000313|Proteomes:UP000006643};
RX PubMed=19741609; DOI=10.1038/nature08358;
RG The Broad Institute Genome Sequencing Platform;
RA Haas B.J., Kamoun S., Zody M.C., Jiang R.H., Handsaker R.E., Cano L.M.,
RA Grabherr M., Kodira C.D., Raffaele S., Torto-Alalibo T., Bozkurt T.O.,
RA Ah-Fong A.M., Alvarado L., Anderson V.L., Armstrong M.R., Avrova A.,
RA Baxter L., Beynon J., Boevink P.C., Bollmann S.R., Bos J.I., Bulone V.,
RA Cai G., Cakir C., Carrington J.C., Chawner M., Conti L., Costanzo S.,
RA Ewan R., Fahlgren N., Fischbach M.A., Fugelstad J., Gilroy E.M., Gnerre S.,
RA Green P.J., Grenville-Briggs L.J., Griffith J., Grunwald N.J., Horn K.,
RA Horner N.R., Hu C.H., Huitema E., Jeong D.H., Jones A.M., Jones J.D.,
RA Jones R.W., Karlsson E.K., Kunjeti S.G., Lamour K., Liu Z., Ma L.,
RA Maclean D., Chibucos M.C., McDonald H., McWalters J., Meijer H.J.,
RA Morgan W., Morris P.F., Munro C.A., O'Neill K., Ospina-Giraldo M.,
RA Pinzon A., Pritchard L., Ramsahoye B., Ren Q., Restrepo S., Roy S.,
RA Sadanandom A., Savidor A., Schornack S., Schwartz D.C., Schumann U.D.,
RA Schwessinger B., Seyer L., Sharpe T., Silvar C., Song J., Studholme D.J.,
RA Sykes S., Thines M., van de Vondervoort P.J., Phuntumart V., Wawra S.,
RA Weide R., Win J., Young C., Zhou S., Fry W., Meyers B.C., van West P.,
RA Ristaino J., Govers F., Birch P.R., Whisson S.C., Judelson H.S.,
RA Nusbaum C.;
RT "Genome sequence and analysis of the Irish potato famine pathogen
RT Phytophthora infestans.";
RL Nature 461:393-398(2009).
CC -!- FUNCTION: Bifunctional enzyme. Involved in de novo dTMP biosynthesis.
CC Key enzyme in folate metabolism. Catalyzes an essential reaction for de
CC novo glycine and purine synthesis, DNA precursor synthesis, and for the
CC conversion of dUMP to dTMP. {ECO:0000256|ARBA:ARBA00025154}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + dUMP = 7,8-
CC dihydrofolate + dTMP; Xref=Rhea:RHEA:12104, ChEBI:CHEBI:15636,
CC ChEBI:CHEBI:57451, ChEBI:CHEBI:63528, ChEBI:CHEBI:246422;
CC EC=2.1.1.45; Evidence={ECO:0000256|ARBA:ARBA00001707};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate +
CC H(+) + NADPH; Xref=Rhea:RHEA:15009, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57451, ChEBI:CHEBI:57453, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=1.5.1.3;
CC Evidence={ECO:0000256|ARBA:ARBA00001315};
CC -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-
CC tetrahydrofolate from 7,8-dihydrofolate: step 1/1.
CC {ECO:0000256|ARBA:ARBA00004903, ECO:0000256|PIRNR:PIRNR000389}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the thymidylate
CC synthase family. {ECO:0000256|ARBA:ARBA00006900,
CC ECO:0000256|PIRNR:PIRNR000389}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the dihydrofolate
CC reductase family. {ECO:0000256|ARBA:ARBA00010176,
CC ECO:0000256|PIRNR:PIRNR000389}.
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DR EMBL; DS028127; EEY53123.1; -; Genomic_DNA.
DR RefSeq; XP_002904741.1; XM_002904695.1.
DR AlphaFoldDB; D0N806; -.
DR STRING; 403677.D0N806; -.
DR EnsemblProtists; PITG_06749T0; PITG_06749T0; PITG_06749.
DR GeneID; 9463079; -.
DR KEGG; pif:PITG_06749; -.
DR VEuPathDB; FungiDB:PITG_06749; -.
DR eggNOG; KOG0673; Eukaryota.
DR eggNOG; KOG1324; Eukaryota.
DR HOGENOM; CLU_021669_2_2_1; -.
DR InParanoid; D0N806; -.
DR OMA; ILCAWNV; -.
DR OrthoDB; 1118873at2759; -.
DR UniPathway; UPA00077; UER00158.
DR Proteomes; UP000006643; Partially assembled WGS sequence.
DR GO; GO:0004146; F:dihydrofolate reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0004799; F:thymidylate synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0006231; P:dTMP biosynthetic process; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd00209; DHFR; 1.
DR CDD; cd00351; TS_Pyrimidine_HMase; 1.
DR Gene3D; 3.40.430.10; Dihydrofolate Reductase, subunit A; 1.
DR Gene3D; 3.30.572.10; Thymidylate synthase/dCMP hydroxymethylase domain; 1.
DR HAMAP; MF_00008; Thymidy_synth_bact; 1.
DR InterPro; IPR024072; DHFR-like_dom_sf.
DR InterPro; IPR012262; DHFR-TS.
DR InterPro; IPR017925; DHFR_CS.
DR InterPro; IPR001796; DHFR_dom.
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; IPR000398; Thymidylate_synthase.
DR InterPro; IPR020940; Thymidylate_synthase_AS.
DR NCBIfam; TIGR03284; thym_sym; 1.
DR PANTHER; PTHR11548:SF2; THYMIDYLATE SYNTHASE; 1.
DR PANTHER; PTHR11548; THYMIDYLATE SYNTHASE 1; 1.
DR Pfam; PF00186; DHFR_1; 1.
DR Pfam; PF00303; Thymidylat_synt; 1.
DR PIRSF; PIRSF000389; DHFR-TS; 1.
DR PRINTS; PR00108; THYMDSNTHASE.
DR SUPFAM; SSF53597; Dihydrofolate reductase-like; 1.
DR SUPFAM; SSF55831; Thymidylate synthase/dCMP hydroxymethylase; 1.
DR PROSITE; PS00075; DHFR_1; 1.
DR PROSITE; PS51330; DHFR_2; 1.
DR PROSITE; PS00091; THYMIDYLATE_SYNTHASE; 1.
PE 3: Inferred from homology;
KW Methyltransferase {ECO:0000256|ARBA:ARBA00022603,
KW ECO:0000256|PIRNR:PIRNR000389};
KW Multifunctional enzyme {ECO:0000256|ARBA:ARBA00023268};
KW NADP {ECO:0000256|ARBA:ARBA00022857};
KW Nucleotide biosynthesis {ECO:0000256|ARBA:ARBA00022727,
KW ECO:0000256|PIRNR:PIRNR000389};
KW One-carbon metabolism {ECO:0000256|ARBA:ARBA00022563,
KW ECO:0000256|PIRNR:PIRNR000389};
KW Oxidoreductase {ECO:0000256|ARBA:ARBA00023002,
KW ECO:0000256|PIRNR:PIRNR000389};
KW Reference proteome {ECO:0000313|Proteomes:UP000006643};
KW Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|PIRNR:PIRNR000389}.
FT DOMAIN 5..184
FT /note="DHFR"
FT /evidence="ECO:0000259|PROSITE:PS51330"
FT ACT_SITE 372
FT /evidence="ECO:0000256|PIRSR:PIRSR000389-1,
FT ECO:0000256|PROSITE-ProRule:PRU10016"
SQ SEQUENCE 509 AA; 57368 MW; 529C2ABA70943459 CRC64;
MTEQSIRVVV AALETTGGIG LRQHIPWRLP SDMKHFRALT TASPDSSVQH AVIMGRKTWE
SLPAKVRPMP KRYNVVLTRD SSYRNKQEIP DTVGVAASFR EALKLVQEQG DKVDQVFVIG
GGAVYAEALS YPSCTKVHLT RVKGQFECDA FFPLEQLEQN FKVAEESEVK EENGVQFHFV
EWERKTGEVK AVESALLVDN TTPHEEMQYL DLIRKILTQG AKREDRTGTG TLSVFGAQMR
FSLRNNVFPL LTTKRVFWRG VAEELLWFIS GDTSAHTLQQ KDIHIWDGNG SREYLDSRGL
QHREVGDLGP VYGFQWRHFG AKYTDMHADY TGKGVDQLAE VIHKLRTNPT DRRIVLSAWN
PSDLNEMALP PCHMFCQFYV ANGELSCQMY QRSADMGLGV PFNIASYALL TRLVAQVTGL
KPGEFIHVIG DAHVYLNHVE PLQKQLTRTP CPFPTLHINP EKTSSIDEFT FEDFEWVSDY
AGSAIVLCKL SWSPSLVGVV YLVKADEGA
//
