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O02604 (DRTS_PLAVI) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 85. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Bifunctional dihydrofolate reductase-thymidylate synthase

Short name=DHFR-TS

Including the following 2 domains:

  1. Dihydrofolate reductase
    EC=1.5.1.3
  2. Thymidylate synthase
    EC=2.1.1.45
OrganismPlasmodium vivax
Taxonomic identifier5855 [NCBI]
Taxonomic lineageEukaryotaAlveolataApicomplexaAconoidasidaHaemosporidaPlasmodiumPlasmodium (Plasmodium)

Protein attributes

Sequence length623 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, DNA precursor synthesis, and for the conversion of dUMP to dTMP. HAMAP-Rule MF_00008

Catalytic activity

5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH. Ref.2

5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP. Ref.2

Pathway

Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate: step 1/1. HAMAP-Rule MF_00008

Subunit structure

Homodimer. Ref.2

Domain

The repeat region is missing in the pyrimethamine-resistant isolates BUR-98 and BUR-151. HAMAP-Rule MF_00008

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 623623Bifunctional dihydrofolate reductase-thymidylate synthase HAMAP-Rule MF_00008
PRO_0000186351

Regions

Domain9 – 237229DHFR
Repeat88 – 9141 HAMAP-Rule MF_00008
Repeat94 – 9742 HAMAP-Rule MF_00008
Repeat100 – 10343 HAMAP-Rule MF_00008
Nucleotide binding38 – 447NADP HAMAP-Rule MF_00008
Nucleotide binding115 – 1173NADP HAMAP-Rule MF_00008
Nucleotide binding137 – 1393NADP HAMAP-Rule MF_00008
Nucleotide binding174 – 1818NADP HAMAP-Rule MF_00008
Nucleotide binding524 – 5285dUMP By similarity
Nucleotide binding566 – 5683dUMP By similarity
Region13 – 142Substrate binding HAMAP-Rule MF_00008
Region88 – 103163 X 4 AA repeats of G-G-D-N HAMAP-Rule MF_00008
Region337 – 623287Thymidylate synthase HAMAP-Rule MF_00008

Sites

Active site5051 By similarity
Binding site151NADP; via amide nitrogen and carbonyl oxygen
Binding site531Substrate
Binding site1531NADP; via carbonyl oxygen
Binding site1731Substrate; via carbonyl oxygen
Binding site1791Substrate
Binding site1941Substrate
Binding site3601dUMP By similarity
Binding site5061dUMP By similarity
Binding site5361dUMP By similarity

Natural variations

Natural variant581S → R in the pyrimethamine-resistant isolates BUR-98 and BUR-151; interferes with inhibitor binding.
Natural variant1171S → N in the pyrimethamine-resistant isolates BUR-98 and BUR-151. Ref.2

Secondary structure

............................................ 623
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O02604 [UniParc].

Last modified May 30, 2000. Version 2.
Checksum: 3E6E958F04FB5828

FASTA62371,057
        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 

« Hide

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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: Isolate Ari/Pakistan, Isolate BUR-151 and Isolate BUR-98.
[2]"Crystal structure of dihydrofolate reductase from Plasmodium vivax: pyrimethamine displacement linked with mutation-induced resistance."
Kongsaeree P., Khongsuk P., Leartsakulpanich U., Chitnumsub P., Tarnchompoo B., Walkinshaw M.D., Yuthavong Y.
Proc. Natl. Acad. Sci. U.S.A. 102:13046-13051(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 1-238 OF WILD TYPE AND MUTANT ARG-58/ASN-117 IN COMPLEXES WITH THE SYNTHETIC INHIBITORS PYR; PYR20 AND WITH NADP, SUBUNIT, CHARACTERIZATION OF PYRIMETHAMINE-RESISTANT VARIANT ASN-117, CATALYTIC ACTIVITY.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X98123 Genomic DNA. Translation: CAA66805.1.
PIRJC6568.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2BL9X-ray1.90A1-238[»]
2BLAX-ray2.50A1-238[»]
2BLBX-ray3.00A1-238[»]
2BLCX-ray2.25A1-238[»]
ProteinModelPortalO02604.
SMRO02604. Positions 2-238, 338-623.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Enzyme and pathway databases

UniPathwayUPA00077; UER00158.

Family and domain databases

Gene3D3.30.572.10. 1 hit.
3.40.430.10. 1 hit.
HAMAPMF_00008. Thymidy_synth_bact.
InterProIPR024072. DHFR-like_dom.
IPR012262. DHFR-TS.
IPR017925. DHFR_CS.
IPR001796. DHFR_dom.
IPR023451. Thymidate_synth/dCMP_Mease.
IPR000398. Thymidylate_synthase.
IPR020940. Thymidylate_synthase_AS.
[Graphical view]
PfamPF00186. DHFR_1. 1 hit.
PF00303. Thymidylat_synt. 1 hit.
[Graphical view]
PIRSFPIRSF000389. DHFR-TS. 1 hit.
PRINTSPR00108. THYMDSNTHASE.
SUPFAMSSF53597. SSF53597. 1 hit.
SSF55831. SSF55831. 1 hit.
TIGRFAMsTIGR03284. thym_sym. 1 hit.
PROSITEPS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
PS00091. THYMIDYLATE_SYNTHASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO02604.

Entry information

Entry nameDRTS_PLAVI
AccessionPrimary (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: February 19, 2014
This is version 85 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways