Reviewed, UniProtKB/Swiss-Prot Q27713 (DRTS_PLABA)

Names and origin

Protein names	Recommended name:     Bifunctional dihydrofolate reductase-thymidylate synthase       Short name=DHFR-TS Including the following 2 domains:     1- Recommended name:             Dihydrofolate reductase               EC=1.5.1.3     2- Recommended name:             Thymidylate synthase               EC=2.1.1.45
Organism	Plasmodium berghei (strain Anka)
Taxonomic identifier	5823 [NCBI]
Taxonomic lineage	Eukaryota › Alveolata › Apicomplexa › Aconoidasida › Haemosporida › Plasmodium › Plasmodium (Vinckeia)

Protein attributes

Sequence length	587 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Inferred from homology.

General annotation (Comments)

Catalytic activity	5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + NADPH. 5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP.
Pathway	Cofactor biosynthesis; tetrahydrofolate biosynthesis; tetrahydrofolate from dihydrofolate: step 1/1.
Miscellaneous	The reaction catalyzed by this enzyme represents an essential step for de novo glycine and purine synthesis, DNA precursor synthesis, and for the conversion of dUMP to dTMP.
Sequence similarities	In the N-terminal section; belongs to the dihydrofolate reductase family. In the C-terminal section; belongs to the thymidylate synthase family. Contains 1 DHFR (dihydrofolate reductase) domain.

Ontologies

Keywords
Biological process	Nucleotide biosynthesis One-carbon metabolism
Ligand	NADP
Molecular function	Methyltransferase Oxidoreductase Transferase
Technical term	Multifunctional enzyme
Gene Ontology (GO)
Biological process	dTMP biosynthetic process Inferred from electronic annotation. Source: InterPro glycine biosynthetic process Inferred from electronic annotation. Source: InterPro one-carbon compound metabolic process Inferred from electronic annotation. Source: InterPro oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	dihydrofolate reductase activity Inferred from electronic annotation. Source: InterPro thymidylate synthase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 587	587	Bifunctional dihydrofolate reductase-thymidylate synthase		PRO_0000186347
Regions
	Domain	9 – 237	229	DHFR
	Region	301 – 587	287	Thymidylate synthase
Sites
	Active site	469	1	By similarity
Natural variations
	Natural variant	110	1	S → N in pyrimethamine resistance.
	Natural variant	177	1	S → F in pyrimethamine resistance.

Sequences

	Sequence		Length	Mass (Da)
	Q27713-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 6E638C2B02FEC13A	FASTA	587	68,932
	10 20 30 40 50 60 MEDLSETFDI YAICACCKVL NDDEKVRCFN NKTFKGIGNA GVLPWKCNLI DMKYFSSVTS 70 80 90 100 110 120 YINENNYIRL KWKRDKYMEK HNLKNNVELN TNIISSTNNL QNIVVMGKKS WESIPKKFKP 130 140 150 160 170 180 LQNRINIILS RTLKKEDIVN ENNNENNNVI IIKSVDDLFP ILKCTKYYKC FIIGGSSVYK 190 200 210 220 230 240 EFLDRNLIKK IYFTRINNSY NCDVLFPEIN ENLFKITSIS DVYYSNNTTL DFIIYSKTKE 250 260 270 280 290 300 INPNEEVPNN TFLGVCDEQN KAFDDEDDYT YFSFNKNKEN IKKNSEHAHN FKIYNSIKYK 310 320 330 340 350 360 NHPEYQYLNI IYDIIMHGNK QDDRTGVGVL SKFGYMMKFN LNEYFPLLTT KKLFIRGIIE 370 380 390 400 410 420 ELLWFIRGET NGNTLLEKNV RIWEANGTRE FLDNRKLFHR EVNDLGPIYG FQWRHFGAEY 430 440 450 460 470 480 TDMHDNYKDK GVDQLKNIIN LIKNDPTCRR IILCAWNVKN LDQMALPPCH ILCQFYVFDG 490 500 510 520 530 540 KLSCIMYQRS CDLGLGVPFN IASYSIFTYM IAQVCNLQAA EFIHVLGNAH VYNNHIESLK 550 560 570 580 IQLNRTPYPF PTLKLNPDIK NIEDFTISDF TVQNYVHHDK INMDMAA

References

[1]	"Mechanisms of pyrimethamine resistance in two different strains of Plasmodium berghei." van Dijk M.R., McConkey G.A., Vinkenoog R., Waters A.P., Janse C.J. Mol. Biochem. Parasitol. 68:167-171(1994) [PubMed: 7891743] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"The dihydrofolate reductase domain of rodent malarias: point mutations and pyrimethamine resistance." Cheng Q., Saul A. Mol. Biochem. Parasitol. 65:361-363(1994) [PubMed: 7969277] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 12-201.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U12275 Genomic DNA. Translation: AAB60237.1. L28119 Genomic DNA. Translation: AAA29581.1.
3D structure databases
HSSP	HSSP built from PDB template 1J3K based on UniProtKB P13922.
SMR	Q27713. Positions 264-587.
ModBase	Search...
Family and domain databases
InterPro	IPR012262. DHFR-TS. IPR001796. DHFR_reg. IPR000398. Thymidylat_synth_C. [Graphical view]
Gene3D	G3DSA:3.30.572.10. Thymidylat_synth_C. 1 hit.
PANTHER	PTHR11549:SF2. Thymidylat_synth_C. 1 hit.
Pfam	PF00186. DHFR_1. 1 hit. PF00303. Thymidylat_synt. 1 hit. [Graphical view]
PIRSF	PIRSF000389. DHFR-TS. 1 hit.
PRINTS	PR00070. DHFR. PR00108. THYMDSNTHASE.
ProDom	PD001180. Thymidylat_synth. 1 hit. [Graphical view] [Entries sharing at least one domain]
TIGRFAMs	TIGR03284. thym_sym. 1 hit.
PROSITE	PS00075. DHFR_1. 1 hit. PS51330. DHFR_2. 1 hit. PS00091. THYMIDYLATE_SYNTHASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00440. Trimethoprim.

Entry information

Entry name

DRTS_PLABA

Accession

Primary (citable) accession number: Q27713
Secondary accession number(s): Q27714

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	November 25, 2008
This is version 47 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)