Reviewed, UniProtKB/Swiss-Prot O02604 (DRTS_PLAVI)

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 vivax
Taxonomic identifier	5855 [NCBI]
Taxonomic lineage	Eukaryota › Alveolata › Apicomplexa › Aconoidasida › Haemosporida › Plasmodium › Plasmodium (Plasmodium)

Protein attributes

Sequence length	623 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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.
Domain	The repeat region is missing in the pyrimethamine-resistant isolates BUR-98 and BUR-151.
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
Domain	Repeat
Ligand	NADP
Molecular function	Methyltransferase Oxidoreductase Transferase
Technical term	3D-structure 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 – 623

623

Bifunctional dihydrofolate reductase-thymidylate synthase

PRO_0000186351

Regions

Domain

9 – 237

229

DHFR

Repeat

88 – 91

4

1

Repeat

94 – 97

4

2

Repeat

100 – 103

4

3

Region

88 – 103

16

3 X 4 AA repeats of G-G-D-N

Region

337 – 623

287

Thymidylate synthase

Sites

Active site

505

1

By similarity

Natural variations

Natural variant

58

1

S → R in the pyrimethamine-resistant isolates BUR-98 and BUR-151.

Natural variant

117

1

S → N in the pyrimethamine-resistant isolates BUR-98 and BUR-151.

Secondary structure

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623

Helix Strand Turn

Details...

Helix

4 – 7

4

Beta strand

10 – 19

10

Beta strand

23 – 26

4

Beta strand

38 – 41

4

Beta strand

46 – 48

3

Helix

51 – 62

12

Helix

66 – 68

3

Helix

69 – 83

15

Beta strand

109 – 114

6

Helix

115 – 119

5

Helix

123 – 125

3

Beta strand

131 – 136

6

Turn

142 – 144

3

Beta strand

150 – 153

4

Helix

155 – 163

9

Beta strand

170 – 174

5

Helix

176 – 184

9

Beta strand

189 – 200

12

Beta strand

203 – 205

3

Helix

211 – 213

3

Beta strand

214 – 219

6

Beta strand

223 – 225

3

Beta strand

228 – 237

10

Sequences

	Sequence		Length	Mass (Da)
	O02604-1 [UniParc]. Last modified May 30, 2000. Version 2. Checksum: 3E6E958F04FB5828	FASTA	623	71,057
	10 20 30 40 50 60 MEDLSDVFDI YAICACCKVA PTSEGTKNEP FSPRTFRGLG NKGTLPWKCN SVDMKYFSSV 70 80 90 100 110 120 TTYVDESKYE KLKWKRERYL RMEASQGGGD NTSGGDNTHG GDNADKLQNV VVMGRSSWES 130 140 150 160 170 180 IPKQYKPLPN RINVVLSKTL TKEDVKEKVF IIDSIDDLLL LLKKLKYYKC FIIGGAQVYR 190 200 210 220 230 240 ECLSRNLIKQ IYFTRINGAY PCDVFFPEFD ESQFRVTSVS EVYNSKGTTL DFLVYSKVGG 250 260 270 280 290 300 GVDGGASNGS TATALRRTAM RSTAMRRNVA PRTAAPPMGP HSRANGERAP PRARARRTTP 310 320 330 340 350 360 RQRKTTSCTS ALTTKWGRKT RSTCKILKFT TASRLMQHPE YQYLGIIYDI IMNGNKQGDR 370 380 390 400 410 420 TGVGVMSNFG YMMKFNLSEY FPLLTTKKLF LRGIIEELLW FIRGETNGNT LLNKNVRIWE 430 440 450 460 470 480 ANGTREFLDN RKLFHREVND LGPIYGFQWR HFGAEYTNMH DNYEDKGVDQ LKNVIHLIKN 490 500 510 520 530 540 EPTSRRIILC AWNVKDLDQM ALPPCHILCQ FYVFDGKLSC IMYQRSCDLG LGVPFNIASY 550 560 570 580 590 600 SIFTHMIAQV CNLQPAQFIH ILGNAHVYNN HVDSLKVQLN RIPYPFPTLK LNPEVKNIED 610 620 FTISDFTIEN YVHHDKITME MAA

References

[1]	"Analysis of the Plasmodium vivax dihydrofolate reductase-thymidylate synthase gene sequence." Eldin de Pecoulas P., Basco L.K., Tahar R., Ouatas T., Mazabraud A. Gene 211:177-185(1998) [PubMed: 9573357] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Isolate Ari/Pakistan, Isolate BUR-151 and Isolate BUR-98.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

X98123 Genomic DNA. Translation: CAA66805.1.

PIR

JC6568.

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2BL9	X-ray	1.90	A	1-238	[»]
2BLA	X-ray	2.50	A	1-238	[»]
2BLB	X-ray	3.00	A	1-238	[»]
2BLC	X-ray	2.25	A	1-238	[»]

SMR

O02604. Positions 338-623.

ModBase

Search...

Enzyme and pathway databases

BRENDA

1.5.1.3. 257191.
2.1.1.45. 257191.

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_PLAVI

Accession

Primary (citable) accession number: O02604
Secondary accession number(s): O15873

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	May 30, 2000
Last modified:	June 16, 2009
This is version 60 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)