ID D2CLW6_9APIC Unreviewed; 639 AA.
AC D2CLW6;
DT 09-FEB-2010, integrated into UniProtKB/TrEMBL.
DT 09-FEB-2010, sequence version 1.
DT 27-MAR-2024, entry version 53.
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};
GN Name=DHFR-TS {ECO:0000313|EMBL:ABY83772.1};
OS Plasmodium ovale (malaria parasite P. ovale).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Plasmodium).
OX NCBI_TaxID=36330 {ECO:0000313|EMBL:ABY83772.1};
RN [1] {ECO:0000313|EMBL:ABY83772.1}
RP NUCLEOTIDE SEQUENCE.
RA Tanomsing N., Imwong M., Pukrittayakamee S., Dolecek C., Hien T.T.,
RA do Rosario V.E., Arez A.P., Pinto J., Michon P., Nosten F., Snounou G.,
RA White N.J., Day N.P.J.;
RT "Sequence variation in the dihydrofolate reductase-thymidylate synthase
RT gene from field isolates of Plasmodium ovale.";
RL Submitted (OCT-2007) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000313|EMBL:ADE75021.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=T21 {ECO:0000313|EMBL:ADE75021.1};
RX PubMed=20380562; DOI=10.1086/652240;
RA Sutherland C.J., Tanomsing N., Nolder D., Oguike M., Jennison C.,
RA Pukrittayakamee S., Dolecek C., Hien T.T., do Rosario V.E., Arez A.P.,
RA Pinto J., Michon P., Escalante A.A., Nosten F., Burke M., Lee R., Blaze M.,
RA Otto T.D., Barnwell J.W., Pain A., Williams J., White N.J., Day N.P.,
RA Snounou G., Lockhart P.J., Chiodini P.L., Imwong M., Polley S.D.;
RT "Two nonrecombining sympatric forms of the human malaria parasite
RT Plasmodium ovale occur globally.";
RL J. Infect. Dis. 201:1544-1550(2010).
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 -!- 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}.
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DR EMBL; EU266603; ABY83772.1; -; Genomic_DNA.
DR EMBL; GQ250091; ADE75021.1; -; Genomic_DNA.
DR AlphaFoldDB; D2CLW6; -.
DR VEuPathDB; PlasmoDB:PocGH01_05028400; -.
DR VEuPathDB; PlasmoDB:POWCR01_050023500; -.
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:InterPro.
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 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.
PE 3: Inferred from homology;
KW Methyltransferase {ECO:0000256|ARBA:ARBA00022603};
KW NADP {ECO:0000256|ARBA:ARBA00022857};
KW One-carbon metabolism {ECO:0000256|ARBA:ARBA00022563};
KW Oxidoreductase {ECO:0000256|ARBA:ARBA00023002};
KW Transferase {ECO:0000256|ARBA:ARBA00022679}.
FT DOMAIN 9..233
FT /note="DHFR"
FT /evidence="ECO:0000259|PROSITE:PS51330"
FT ACT_SITE 521
FT /evidence="ECO:0000256|PIRSR:PIRSR000389-1"
SQ SEQUENCE 639 AA; 73663 MW; A7A084E9F416CD66 CRC64;
MEQLSDVFDI YAICACCKVS KEGDWKKSES FSSSTFRGIG NKGILPWKCN SVDISYFSSV
TTYVNEWNYK KLKYKREKYL EKDISNDKKK VDVINIAPIS KKLQNVVVMG RSSWESIPKS
YKPLANRINV VLSSTLKKED VKEDIFIMKS MDEVLLLLKK LYYYKCFIIG GAGVYKECLE
RNLIKQIYLT RINNTYECDV FFPDMDENAF QITSVSEVYS SNGTTLDFLI YSRKKKDTQN
DGDSSEGSTT TTATATATWP GIAGATSSMN IAETSTTFAS SHHGKGSSKW WTKGCTKGGA
EWWGNMALTS QGKDNVDDED DYMYFSFNNK KKKSQIMKNV EDFEIYNSIK LKQHPEYQYL
NIIYDVMMNG NKQDDRTGVG VLSKFGYMMK YNLAEYFPLL TTKKLFVRGI IEELLWFIRG
ETNGNILLNK NVRIWEANGT REFLDNRKLF DREVNDLGPI YGFQWRHFGA EYTNMYDNYE
NKGIDQLKNI INLIKNEPTS RRIILCAWNV KDLDKMALPP CHILCQFYIF DGKLSCIMYQ
RSCDLGLGVP FNIASYSIFT YMLAQVCNLQ PAEFIHVLGN AHIYNNHIDS LKIQLNRIPY
PFPTLKLNPE IKNIEDFTIS DFTIENYVHH DKITMDMAA
//
