ID U3M187_9APIC Unreviewed; 612 AA.
AC U3M187;
DT 11-DEC-2013, integrated into UniProtKB/TrEMBL.
DT 11-DEC-2013, sequence version 1.
DT 13-SEP-2023, entry version 30.
DE RecName: Full=Bifunctional dihydrofolate reductase-thymidylate synthase {ECO:0000256|ARBA:ARBA00019798};
DE EC=1.5.1.3 {ECO:0000256|ARBA:ARBA00012856};
DE EC=2.1.1.45 {ECO:0000256|ARBA:ARBA00011947};
DE Flags: Fragment;
GN Name=dhfr-ts {ECO:0000313|EMBL:AGR88686.1};
OS Plasmodium coatneyi.
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium.
OX NCBI_TaxID=208452 {ECO:0000313|EMBL:AGR88686.1};
RN [1] {ECO:0000313|EMBL:AGR88686.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=24044371;
RA Pacheco M.A., Cranfield M., Cameron K., Escalante A.A.;
RT "Malarial parasite diversity in chimpanzees: the value of comparative
RT approaches to ascertain the evolution of Plasmodium falciparum antigens.";
RL Malar. J. 12:328-328(2013).
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}.
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 -!- SIMILARITY: In the N-terminal section; belongs to the dihydrofolate
CC reductase family. {ECO:0000256|ARBA:ARBA00010176}.
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DR EMBL; JX893159; AGR88686.1; -; Genomic_DNA.
DR AlphaFoldDB; U3M187; -.
DR VEuPathDB; PlasmoDB:PCOAH_00012090; -.
DR UniPathway; UPA00077; UER00158.
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 Multifunctional enzyme {ECO:0000256|ARBA:ARBA00023268};
KW NADP {ECO:0000256|ARBA:ARBA00022857};
KW Nucleotide biosynthesis {ECO:0000256|ARBA:ARBA00022727};
KW One-carbon metabolism {ECO:0000256|ARBA:ARBA00022563};
KW Oxidoreductase {ECO:0000256|ARBA:ARBA00023002};
KW Transferase {ECO:0000256|ARBA:ARBA00022679}.
FT DOMAIN 1..225
FT /note="DHFR"
FT /evidence="ECO:0000259|PROSITE:PS51330"
FT ACT_SITE 494
FT /evidence="ECO:0000256|PIRSR:PIRSR000389-1,
FT ECO:0000256|PROSITE-ProRule:PRU10016"
FT NON_TER 1
FT /evidence="ECO:0000313|EMBL:AGR88686.1"
SQ SEQUENCE 612 AA; 69711 MW; 6020A23FD960C4E0 CRC64;
ICACCKVAPP SEGIKNEPFG PRTFRGLGNN GALPWKCNSV DMKYFSSVTT YVDESKYEKL
KWKREKYLQG EASGGSVANH SNGNPVGMGD NTVKLQNVVV MGRSSWESIP KQYKPLPNRI
NVVLSKTLTN EQVKEKVFII HSIDELLLLL KKLRYYKCFI IGGAQVYKEC LNRNLIKQIY
FTRINNTYPC DVLFPEIDEG QFKVTSVSEV YNSKGTTLDF VIYSKVGGEV DGIASNGSTV
DSGSENCENV KCGAPNCSVS GCISPNCTIT QQEEWGKCSP ACQQQKNNAV VEEDDLVYFS
FNNKVGEKNP EHLNDFKIYN SLKIKQHPEY QYLSIIYDII MNGNKQGDRT GVGVVSKFGY
MMKFNLNEYF PLLTTKKLFL RGIIEELLWF IRGETNGNTL LKKNVRIWEA NGTREFLDNR
KLFHREVNDL GPIYGFQWRH FGAEYTNMHD NYEDKGVDQL KNVIHLIKNE PTSRRIILCA
WNVKDLDQMA LPPCHILCQF YVFDGKLSCI MYQRSCDLGL GVPFNIASYS IFTHMIAQVC
NLQPAQFIHI LGNAHVYNNH IDSLKVQLNR IPYPFPTLKL NPEVKNIEDF TISDFTIENY
VHHDKIAMDM AA
//
