ID D2CLY1_9APIC Unreviewed; 622 AA.
AC D2CLY1;
DT 09-FEB-2010, integrated into UniProtKB/TrEMBL.
DT 09-FEB-2010, sequence version 1.
DT 27-MAR-2024, entry version 50.
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:ABY83787.1};
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:ABY83787.1};
RN [1] {ECO:0000313|EMBL:ABY83787.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=T23 {ECO:0000313|EMBL:ABY83787.1};
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; EU266618; ABY83787.1; -; Genomic_DNA.
DR AlphaFoldDB; D2CLY1; -.
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 1..224
FT /note="DHFR"
FT /evidence="ECO:0000259|PROSITE:PS51330"
FT ACT_SITE 512
FT /evidence="ECO:0000256|PIRSR:PIRSR000389-1"
FT NON_TER 1
FT /evidence="ECO:0000313|EMBL:ABY83787.1"
FT NON_TER 622
FT /evidence="ECO:0000313|EMBL:ABY83787.1"
SQ SEQUENCE 622 AA; 71736 MW; 54D296979A31C601 CRC64;
IYAICACCKV SKEGDWKKSE SFSSSTFRGI GNKGILPWKC NSVDISYFSS VTTYVNEWNY
KKLKYKREKY LEKDISNDKK KVDVINIAPI SKKLQNVVVM GRSSWESIPK SYKPLANRIN
VVLSSTLKKE DVKEDIFIMK SMDEVLLLLK KLYYYKCFII GGAGVYKECL ERNLIKQIYL
TRINNTYECD VFFPDMDENA FQITSVSEVY SSNGTTLDFL IYSRKKKDTQ NDGDSSEGST
TTTATATATW PGIAGATSSM NIAETSTTFA SSHHGKGSSK WWTKGCTKGG AEWWGNMALT
SQGKDNVDDE DDYMYFSFNN KKKKSQIMKN VEDFEIYNSI KLKQHPEYQY LNIIYDVMMN
GNKQDDRTGV GVLSKFGYMM KYNLAEYFPL LTTKKLFVRG IIEELLWFIR GETNGNILLN
KNVRIWEANG TREFLDNRKL FDREVNDLGP IYGFQWRHFG AEYTNMYDNY ENKGIDQLKN
IINLIKNEPT SRRIILCAWN VKDLDKMALP PCHILCQFYI FDGKLSCIMY QRSCDLGLGV
PFNIASYSIF TYMLAQVCNL QPAEFIHVLG NAHIYNNHID SLKIQLNRIP YPFPTLKLNP
EIKNIEDFTI SDFTIENYVH HD
//
