ID A0A6A4D3W2_9STRA Unreviewed; 488 AA.
AC A0A6A4D3W2;
DT 17-JUN-2020, integrated into UniProtKB/TrEMBL.
DT 17-JUN-2020, sequence version 1.
DT 13-SEP-2023, entry version 7.
DE RecName: Full=Bifunctional dihydrofolate reductase-thymidylate synthase {ECO:0000256|ARBA:ARBA00019798, ECO:0000256|PIRNR:PIRNR000389};
GN ORFNames=PR001_g21324 {ECO:0000313|EMBL:KAE8991089.1}, PR003_g22455
GN {ECO:0000313|EMBL:KAE9301685.1};
OS Phytophthora rubi.
OC Eukaryota; Sar; Stramenopiles; Oomycota; Peronosporales; Peronosporaceae;
OC Phytophthora.
OX NCBI_TaxID=129364 {ECO:0000313|EMBL:KAE9301685.1, ECO:0000313|Proteomes:UP000434957};
RN [1] {ECO:0000313|EMBL:KAE9301685.1, ECO:0000313|Proteomes:UP000434957}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SCRP249 {ECO:0000313|EMBL:KAE8991089.1,
RC ECO:0000313|Proteomes:UP000429607}, and SCRP333
RC {ECO:0000313|EMBL:KAE9301685.1, ECO:0000313|Proteomes:UP000434957};
RA Adams T.M., Armitage A.D., Sobczyk M.K., Bates H.J., Dunwell J.M.,
RA Nellist C.F., Harrison R.J.;
RT "Genomic investigation of the strawberry pathogen Phytophthora fragariae
RT indicates pathogenicity is determined by transcriptional variation in three
RT key races.";
RL Submitted (AUG-2018) to the EMBL/GenBank/DDBJ databases.
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}.
CC -!- CAUTION: The sequence shown here is derived from an EMBL/GenBank/DDBJ
CC whole genome shotgun (WGS) entry which is preliminary data.
CC {ECO:0000313|EMBL:KAE9301685.1}.
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DR EMBL; QXFV01002213; KAE8991089.1; -; Genomic_DNA.
DR EMBL; QXFT01002227; KAE9301685.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A6A4D3W2; -.
DR UniPathway; UPA00077; UER00158.
DR Proteomes; UP000429607; Unassembled WGS sequence.
DR Proteomes; UP000434957; Unassembled 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:UP000434957};
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 369
FT /evidence="ECO:0000256|PIRSR:PIRSR000389-1,
FT ECO:0000256|PROSITE-ProRule:PRU10016"
SQ SEQUENCE 488 AA; 54820 MW; 96677DF93F9BAEF6 CRC64;
MSERSVRVVV AALEATGGIG LRQQIPWRLP SDMKHFRALT TAPASSSAQH AVIMGRKTWE
SLPTKVRPMP QRYNVVLTRD ASYRQSQGVP DSVGVAASFL EALELVQQQG QKVDQVFVIG
GGAVYAEALA YTGCNKVHLT RVKGAFECDA FFPLEQLKQN FKVTHESELK EENGVQFQFV
EWERKTEEVE TTTLTDSTMP HEEMQYLDLI RKILTQGAKR GDRTGTGTLS VFGAQMRFSL
RGNVFPLLTT KRVFWRGVAE ELLWFISGDT SAHTLQEKDI HIWDGNGSRE YLDSRGLQSR
EVGDLGPVYG FQWRHFGAKY TDMHADYTGQ GVDQLAEVID KLRTNPTDRR IVLSAWNPAD
LNEMALPPCH MFCQFYVADG ELSCQMYQRS ADMGLGVPFN IASYALLTRL IAQVSGLKPG
EFVHVIGDAH VYLNHVEPLQ KQLTRSPRPF PTLHVNPEKT ASIDDFTFED LEVRDYSPHG
TIKMAMSV
//
