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Database: UniProt
Entry: A8C556_PLAMA
LinkDB: A8C556_PLAMA
Original site: A8C556_PLAMA 
ID   A8C556_PLAMA            Unreviewed;       226 AA.
AC   A8C556;
DT   13-NOV-2007, integrated into UniProtKB/TrEMBL.
DT   13-NOV-2007, sequence version 1.
DT   24-JAN-2024, entry version 39.
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;
OS   Plasmodium malariae.
OC   Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC   Plasmodiidae; Plasmodium; Plasmodium (Plasmodium).
OX   NCBI_TaxID=5858 {ECO:0000313|EMBL:ABQ23927.1};
RN   [1] {ECO:0000313|EMBL:ABQ23927.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=Af96 {ECO:0000313|EMBL:ABQ23927.1};
RX   PubMed=17682097; DOI=10.1128/AAC.00234-07;
RA   Tanomsing N., Imwong M., Pukrittayakamee S., Chotivanich K.,
RA   Looareesuwan S., Mayxay M., Dolecek C., Hien T.T., do Rosario V.E.,
RA   Arez A.P., Michon P., Snounou G., White N.J., Day N.P.;
RT   "Genetic analysis of the dihydrofolate reductase-thymidylate synthase gene
RT   from geographically diverse isolates of Plasmodium malariae.";
RL   Antimicrob. Agents Chemother. 51:3523-3530(2007).
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}.
CC   -!- SIMILARITY: Belongs to the dihydrofolate reductase family.
CC       {ECO:0000256|RuleBase:RU004474}.
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DR   EMBL; EF206334; ABQ23927.1; -; Genomic_DNA.
DR   AlphaFoldDB; A8C556; -.
DR   UniPathway; UPA00077; UER00158.
DR   GO; GO:0004146; F:dihydrofolate reductase activity; IEA:UniProtKB-EC.
DR   GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR   GO; GO:0004799; F:thymidylate synthase activity; IEA:UniProtKB-EC.
DR   GO; GO:0006545; P:glycine biosynthetic process; IEA:InterPro.
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   Gene3D; 3.40.430.10; Dihydrofolate Reductase, subunit A; 1.
DR   InterPro; IPR012259; DHFR.
DR   InterPro; IPR024072; DHFR-like_dom_sf.
DR   InterPro; IPR017925; DHFR_CS.
DR   InterPro; IPR001796; DHFR_dom.
DR   PANTHER; PTHR48069; DIHYDROFOLATE REDUCTASE; 1.
DR   PANTHER; PTHR48069:SF3; DIHYDROFOLATE REDUCTASE; 1.
DR   Pfam; PF00186; DHFR_1; 1.
DR   PRINTS; PR00070; DHFR.
DR   SUPFAM; SSF53597; Dihydrofolate reductase-like; 1.
DR   PROSITE; PS00075; DHFR_1; 1.
DR   PROSITE; PS51330; DHFR_2; 1.
PE   3: Inferred from homology;
KW   NADP {ECO:0000256|ARBA:ARBA00022857};
KW   One-carbon metabolism {ECO:0000256|ARBA:ARBA00022563};
KW   Oxidoreductase {ECO:0000256|ARBA:ARBA00023002}.
FT   DOMAIN          1..226
FT                   /note="DHFR"
FT                   /evidence="ECO:0000259|PROSITE:PS51330"
FT   NON_TER         1
FT                   /evidence="ECO:0000313|EMBL:ABQ23927.1"
FT   NON_TER         226
FT                   /evidence="ECO:0000313|EMBL:ABQ23927.1"
SQ   SEQUENCE   226 AA;  26248 MW;  E5279FD7BBDE49D4 CRC64;
     DIYAICACCK VPNHGEGKKN EIFSTKTFRG LGNKGCLPWE SNSLDMKYFS SVTTYVNEMK
     YKKLKYKREK YLEKEISNEN SSTVFENISL LSSSKLQNVV VMGRSSWVSI PKQYKPLPNR
     INVVLSRTLK KEDVKEDIFI INNMDQLVLL LKKLNYYKCF IIGGAIVYKE CLERNLIKQI
     YFTRINNVYE CDVFFPEIDE NVFQITSVSD VYTSNCTSLD FVIFSK
//
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