ID A0A662WM23_9STRA Unreviewed; 492 AA.
AC A0A662WM23;
DT 22-APR-2020, integrated into UniProtKB/TrEMBL.
DT 22-APR-2020, sequence version 1.
DT 13-SEP-2023, entry version 10.
DE RecName: Full=Bifunctional dihydrofolate reductase-thymidylate synthase {ECO:0000256|ARBA:ARBA00019798, ECO:0000256|PIRNR:PIRNR000389};
GN ORFNames=BBJ28_00005181 {ECO:0000313|EMBL:RLN32214.1};
OS Nothophytophthora sp. Chile5.
OC Eukaryota; Sar; Stramenopiles; Oomycota; Peronosporales; Peronosporaceae;
OC Nothophytophthora.
OX NCBI_TaxID=2483409 {ECO:0000313|EMBL:RLN32214.1, ECO:0000313|Proteomes:UP000274840};
RN [1] {ECO:0000313|EMBL:RLN32214.1, ECO:0000313|Proteomes:UP000274840}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Chile5 {ECO:0000313|EMBL:RLN32214.1};
RA Studholme D.J., Sanfuentes E., Panda P., Hill R., Sambles C., Grant M.,
RA Williams N.M., Mcdougal R.L.;
RT "Genome sequencing of oomycete isolates from Chile give support for New
RT Zealand origin for Phytophthora kernoviae and make available the first
RT Nothophytophthora sp. genome.";
RL Submitted (JUL-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:RLN32214.1}.
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DR EMBL; MBAC02010380; RLN32214.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A662WM23; -.
DR UniPathway; UPA00077; UER00158.
DR Proteomes; UP000274840; Unassembled WGS sequence.
DR GO; GO:0004146; F:dihydrofolate reductase activity; IEA:InterPro.
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:UP000274840};
KW Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|PIRNR:PIRNR000389}.
FT DOMAIN 5..185
FT /note="DHFR"
FT /evidence="ECO:0000259|PROSITE:PS51330"
FT ACT_SITE 373
FT /evidence="ECO:0000256|PIRSR:PIRSR000389-1,
FT ECO:0000256|PROSITE-ProRule:PRU10016"
SQ SEQUENCE 492 AA; 55004 MW; 8E81BB2B1431A254 CRC64;
MTPRSVHVVV AAAEANGGIG FRQQIPWRLP TDMKRFRALT VRAPATETPQ HAVVMGRKTW
ESLPAKVRPL PQRYNVVLTR NASYRQSADV PESVGVAASF REALALIQAK GDAVDQVFVI
GGGAVYAEAL AYEGCSHVHL TRVKGDFVCD AFFPSDLKTR GFQIVSESEI KEENGVQFQF
VDLEREVSAE TPRVEAPLLD NTTPHEETQY LALIRQILTQ GARRGDRTGT GTLSVFGAQM
RFNLRDNVFP LLTTKRVFWR GVAEELLWFI SGDTNAATLQ QKDIHIWDGN GSREYLDSRG
LQARETGDLG PVYGFQWRHF GAKYTNMHAD YTGQGVDQLA EVIQKLRTNP SDRRIVLSAW
NPADLNEMAL PPCHMFCQFY VADGELSCQM YQRSADMGLG VPFNIASYAL LTRLVAQVAG
LQPGEFIHVI GDAHVYLNHV EPLQQQLTRT PRPFPTLHLN PEKTSSIDEF AYEDLEVRDY
RPHGAIKMAM SV
//
