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Reviewed, UniProtKB/Swiss-Prot P13922 (DRTS_PLAFK)

Last modified June 16, 2009. Version 74. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended 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
OrganismPlasmodium falciparum (isolate K1 / Thailand)
Taxonomic identifier5839 [NCBI]
Taxonomic lineageEukaryota › Alveolata › Apicomplexa › Aconoidasida › Haemosporida › Plasmodium › Plasmodium (Laverania)

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Protein attributes

Sequence length608 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

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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

K1 is from a pyrimethamine-resistant strain; FCR3 is a pyrimethamine-sensitive strain.

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.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 608608Bifunctional dihydrofolate reductase-thymidylate synthase
PRO_0000186349

Regions

Domain10 – 228219DHFR
Region322 – 608287Thymidylate synthase

Sites

Active site4901 By similarity

Natural variations

Natural variant161A → V in strain: Isolate Palo-Alto.
Natural variant511N → I
Natural variant591R → C in strain: Isolate FCR-3, Isolate Gambia and Isolate Palo-Alto.
Natural variant1081N → T in strain: Isolate FCR-3, Isolate Gambia and Isolate Palo-Alto.

Secondary structure

1 ......................................................................................... 608
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
P13922-1 [UniParc].

Last modified August 1, 1990. Version 2.
Checksum: 7727EEB4A3946996

FASTA60871,817
        10         20         30         40         50         60 
MMEQVCDVFD IYAICACCKV ESKNEGKKNE VFNNYTFRGL GNKGVLPWKC NSLDMKYFRA 

        70         80         90        100        110        120 
VTTYVNESKY EKLKYKRCKY LNKETVDNVN DMPNSKKLQN VVVMGRTNWE SIPKKFKPLS 

       130        140        150        160        170        180 
NRINVILSRT LKKEDFDEDV YIINKVEDLI VLLGKLNYYK CFIIGGSVVY QEFLEKKLIK 

       190        200        210        220        230        240 
KIYFTRINST YECDVFFPEI NENEYQIISV SDVYTSNNTT LDFIIYKKTN NKMLNEQNCI 

       250        260        270        280        290        300 
KGEEKNNDMP LKNDDKDTCH MKKLTEFYKN VDKYKINYEN DDDDEEEDDF VYFNFNKEKE 

       310        320        330        340        350        360 
EKNKNSIHPN DFQIYNSLKY KYHPEYQYLN IIYDIMMNGN KQSDRTGVGV LSKFGYIMKF 

       370        380        390        400        410        420 
DLSQYFPLLT TKKLFLRGII EELLWFIRGE TNGNTLLNKN VRIWEANGTR EFLDNRKLFH 

       430        440        450        460        470        480 
REVNDLGPIY GFQWRHFGAE YTNMYDNYEN KGVDQLKNII NLIKNDPTSR RILLCAWNVK 

       490        500        510        520        530        540 
DLDQMALPPC HILCQFYVFD GKLSCIMYQR SCDLGLGVPF NIASYSIFTH MIAQVCNLQP 

       550        560        570        580        590        600 
AQFIHVLGNA HVYNNHIDSL KIQLNRIPYP FPTLKLNPDI KNIEDFTISD FTIQNYVHHE 


KISMDMAA

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References

[1]"Characterisation of the dihydrofolate reductase-thymidylate synthetase gene from human malaria parasites highly resistant to pyrimethamine."
Snewin V.A., England S.M., Sims P.F.G., Hyde J.E.
Gene 76:41-52(1989) [PubMed: 2663650] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: Isolate FCR3 and Isolate K1.
[2]"Point mutations in the dihydrofolate reductase-thymidylate synthase gene as the molecular basis for pyrimethamine resistance in Plasmodium falciparum."
Zolg J.W., Plitt J.R., Chen G.-X., Palmer S.
Mol. Biochem. Parasitol. 36:253-262(1989) [PubMed: 2677719] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Amino acid changes linked to pyrimethamine resistance in the dihydrofolate reductase-thymidylate synthase gene of Plasmodium falciparum."
Cowman A.F., Morry M.J., Biggs B.A., Cross G.A.M., Foote S.J.
Proc. Natl. Acad. Sci. U.S.A. 85:9109-9113(1988) [PubMed: 3057499] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: Isolate Palo-Alto.
[4]"Molecular cloning and sequence analysis of the Plasmodium falciparum dihydrofolate reductase-thymidylate synthase gene."
Bzik D.J., Li W.B., Horii T., Inselburg J.
Proc. Natl. Acad. Sci. U.S.A. 84:8360-8364(1987) [PubMed: 2825189] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: Isolate FCR3.
+Additional computationally mapped references.

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Cross-references

Sequence databases

M22159 Genomic DNA. Translation: AAA29580.1.
J04643 Genomic DNA. Translation: AAA29586.1.
J03772 Genomic DNA. Translation: AAB59212.1.
J03028 Genomic DNA. Translation: AAA29585.1.
PIRRDZQK1. A39975.

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1J3IX-ray2.33A/B1-280[»]
C/D281-608[»]
1J3JX-ray2.30A/B1-280[»]
C/D281-608[»]
1J3KX-ray2.10A/B1-280[»]
C/D281-608[»]
3DG8X-ray2.58A/B1-280[»]
C/D281-608[»]
3DGAX-ray2.70A/B1-280[»]
C/D281-608[»]
ModBaseSearch...

Family and domain databases

InterProIPR012262. DHFR-TS.
IPR001796. DHFR_reg.
IPR017925. Dihydrofolate_reductase_CS.
IPR000398. Thymidylat_synth_C.
[Graphical view]
Gene3DG3DSA:3.30.572.10. Thymidylat_synth_C. 1 hit.
PANTHERPTHR11549:SF2. Thymidylat_synth_C. 1 hit.
PfamPF00186. DHFR_1. 1 hit.
PF00303. Thymidylat_synt. 1 hit.
[Graphical view]
PIRSFPIRSF000389. DHFR-TS. 1 hit.
PRINTSPR00108. THYMDSNTHASE.
ProDomPD001180. Thymidylat_synth. 1 hit.
[Graphical view] [Entries sharing at least one domain]
TIGRFAMsTIGR03284. thym_sym. 1 hit.
PROSITEPS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
PS00091. THYMIDYLATE_SYNTHASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB01131. Proguanil.
DB00205. Pyrimethamine.

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Entry information

Entry nameDRTS_PLAFK
AccessionPrimary (citable) accession number: P13922
Secondary accession number(s): Q27734
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: August 1, 1990
Last modified: June 16, 2009
This is version 74 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)

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Relevant documents

PATHWAY comments

Index of metabolic and biosynthesis pathways

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents