ID Q95US9_PLAGA Unreviewed; 589 AA.
AC Q95US9;
DT 01-DEC-2001, integrated into UniProtKB/TrEMBL.
DT 01-DEC-2001, sequence version 1.
DT 27-MAR-2024, entry version 98.
DE RecName: Full=Bifunctional dihydrofolate reductase-thymidylate synthase {ECO:0000256|ARBA:ARBA00019798, ECO:0000256|PIRNR:PIRNR000389};
GN Name=DHFR/TS {ECO:0000313|EMBL:AAK55761.1};
GN ORFNames=PGAL8A_00090700 {ECO:0000313|EMBL:CRG93203.1};
OS Plasmodium gallinaceum.
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Haemamoeba).
OX NCBI_TaxID=5849 {ECO:0000313|EMBL:AAK55761.1};
RN [1] {ECO:0000313|EMBL:AAK55761.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=11748966; DOI=10.1006/expr.2001.4644;
RA Peterson D.S.;
RT "Plasmodium gallinaceum: cloning and characterization of dihydrofolate
RT reductase/thymidylate synthase.";
RL Exp. Parasitol. 99:111-114(2001).
RN [2] {ECO:0000313|EMBL:CRG93203.1, ECO:0000313|Proteomes:UP000220797}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=8A {ECO:0000313|EMBL:CRG93203.1,
RC ECO:0000313|Proteomes:UP000220797};
RG Pathogen Informatics;
RL Submitted (APR-2015) 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 -!- SUBUNIT: Homodimer. {ECO:0000256|ARBA:ARBA00011738}.
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; AY033582; AAK55761.1; -; Genomic_DNA.
DR EMBL; CVMV01000014; CRG93203.1; -; Genomic_DNA.
DR AlphaFoldDB; Q95US9; -.
DR VEuPathDB; PlasmoDB:PGAL8A_00090700; -.
DR OMA; ILCAWNV; -.
DR OrthoDB; 1118873at2759; -.
DR UniPathway; UPA00077; UER00158.
DR Proteomes; UP000220797; 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; 6.10.250.2210; -; 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 Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|PIRNR:PIRNR000389}.
FT DOMAIN 9..229
FT /note="DHFR"
FT /evidence="ECO:0000259|PROSITE:PS51330"
FT ACT_SITE 471
FT /evidence="ECO:0000256|PIRSR:PIRSR000389-1,
FT ECO:0000256|PROSITE-ProRule:PRU10016"
SQ SEQUENCE 589 AA; 69209 MW; 39067D7E3A1ACB14 CRC64;
MNEISDIFDI HAICACCKVE NKNEKKKNEI FSNNTFRGIG NKGVLPWKSN PLDMKYFTTV
TTYVNESKYK KLKYKREKYL EKTKDTKCLE SIIQLSNNLQ NVVVMGRTSW ESIPERFRPL
VNRINVVLSR SLKKEDIKGD AILINNVDDL LLLLRKINYY KCFIIGGSVV YNEFLKRNLI
KKIYFTRINS TYECDVFFPE IKETEFEIMS LSDVYSNNGA TLDFVIYKRK KEILNNENPI
ENNKEADICS QDSPNNYFTG EDVYKNMDDD DDYVYFNFNN TKEKKNSEIS DDFKIYNSLK
YKYHPEYQYL NIIYDVIMNG NKQGDRTGVG VVSKFGYMMK FNLNQYFPLL TTKKLFIRGI
IEELLWFIRG ETNGNTLLNK NVRIWEANGT REFLDKRKLF DREVNDLGPI YGFQWRHFGA
EYTNMHDNYE NKGVDQLKNI INLIKNEPTS RRIILCAWNV KDLDKMALPP CHILCQFYVF
DNKLSCIMYQ RSCDLGLGVP FNIASYSIFT YMIAQVCNLQ PAQFIHILGN AHVYNNHIDS
LKKQLNRIPY PFPTLKLNPD IKNIEDFKVS DFTIENYVHH DKISMDMAA
//