Reviewed, UniProtKB/Swiss-Prot P20712 (DRTS_PLACH)

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 chabaudi
Taxonomic identifier	5825 [NCBI]
Taxonomic lineage	Eukaryota › Alveolata › Apicomplexa › Aconoidasida › Haemosporida › Plasmodium › Plasmodium (Vinckeia)

Protein attributes

Sequence length	583 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: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	dihydrofolate reductase activity Inferred from electronic annotation. Source: EC thymidylate synthase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 583	583	Bifunctional dihydrofolate reductase-thymidylate synthase		PRO_0000186348
Regions
	Domain	9 – 229	221	DHFR
	Region	298 – 583	286	Thymidylate synthase
Sites
	Active site	465	1	By similarity
Natural variations
	Natural variant	106	1	S → I in pyrimethamine resistance.
Experimental info
	Sequence conflict	27	1	G → S in AAB59201. Ref.2
	Sequence conflict	156	1	C → S in AAB59201. Ref.2
	Sequence conflict	164	1	I → V in AAB59201. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P20712-1 [UniParc]. Last modified February 1, 1991. Version 1. Checksum: 4AA55E1C987E6FD7	FASTA	583	68,051
	10 20 30 40 50 60 MEDISEIFDI YAICACCKVL NSNEKAGCFS NKTFKGLGNE GGLPWKCNSV DMKHFSSVTS 70 80 90 100 110 120 YVNETNYMRL KWKRDRYMEK NNVKLNTDGI PSVDKLQNIV VMGKASWESI PSKFKPLQNR 130 140 150 160 170 180 INIILSRTLK KEDLAKEYNN VIIINSVDDL FPILKCIKYY KCFIIGGASV YKEFLDRNLI 190 200 210 220 230 240 KKIYFTRINN AYTCDVLFPD INEDLFKITS ISDVYSSNNT TLDFVIYSKT KEIHEEINPN 250 260 270 280 290 300 DELFNNTFLG VCDEKNTNFD DEDDYTYFSF NKHKDNIKKN SEHAHHFKIY NSIKYKHHPE 310 320 330 340 350 360 YQYLNIIYDI IMHGNKQDDR TGVGVLSKFG YMMKFNLSEY FPLLTTKKLF VRGIIEELLW 370 380 390 400 410 420 FIRGETNGNT LLEKNVRIWE ANGTREFLDN RKLFHREVND LGPIYGFQWR HFGAEYTDMH 430 440 450 460 470 480 ADYKDKGVDQ LKNIINLIKN DPTCRRIILC AWNVKDLDQM ALPPCHILCQ FYVFDGKLSC 490 500 510 520 530 540 IMYQRSCDLG LGVPFNIASY SIFTYMIAQV CNLQPAEFIH VLGNAHVYNN HVESLKVQLN 550 560 570 580 RTPYPFPTLK LNPEIKNIED FTISDFTVQN YVHHDKISMD MAA

References

[1]	"Antifolate drug selection results in duplication and rearrangement of chromosome 7 in Plasmodium chabaudi." Cowman A.F., Lew A.M. Mol. Cell. Biol. 9:5182-5188(1989) [PubMed: 2601715] [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 12-193.

Cross-references

Sequence databases
EMBLGenBankDDBJ	M30834 Genomic DNA. Translation: AAA29587.1. L28120 Genomic DNA. Translation: AAB59201.1.
PIR	RDZQTB. A33484.
3D structure databases
HSSP	HSSP built from PDB template 1J3K based on UniProtKB P13922.
SMR	P20712. Positions 260-583.
ModBase	Search...
Enzyme and pathway databases
BRENDA	1.5.1.3. 268051. 2.1.1.45. 268051.
Family and domain databases
InterPro	IPR012262. DHFR-TS. IPR001796. DHFR_reg. IPR017925. Dihydrofolate_reductase_CS. 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	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...

Entry information

Entry name

DRTS_PLACH

Accession

Primary (citable) accession number: P20712
Secondary accession number(s): Q27715

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	February 1, 1991
Last modified:	June 16, 2009
This is version 58 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)