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Q27713 (DRTS_PLABA) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 74. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
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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. Dihydrofolate reductase
    EC=1.5.1.3
  2. Thymidylate synthase
    EC=2.1.1.45
OrganismPlasmodium berghei (strain Anka)
Taxonomic identifier5823 [NCBI]
Taxonomic lineageEukaryota › Alveolata › Apicomplexa › Aconoidasida › Haemosporida › Plasmodium › Plasmodium (Vinckeia) ›

Protein attributes

Sequence length587 AA.
Sequence statusComplete.
Protein existenceInferred from homology

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 By similarity.

Catalytic activity

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

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

Pathway

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

Subunit structure

Homodimer By similarity.

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 – 587587Bifunctional dihydrofolate reductase-thymidylate synthase
PRO_0000186347

Regions

Domain9 – 237229DHFR
Nucleotide binding36 – 427NADP By similarity
Nucleotide binding108 – 1103NADP By similarity
Nucleotide binding129 – 1324NADP By similarity
Nucleotide binding174 – 1818NADP By similarity
Nucleotide binding488 – 4925dUMP By similarity
Nucleotide binding530 – 5323dUMP By similarity
Region301 – 587287Thymidylate synthase

Sites

Active site4691 By similarity
Binding site511Substrate By similarity
Binding site1731Substrate; via carbonyl oxygen By similarity
Binding site1791Substrate By similarity
Binding site1941Substrate By similarity
Binding site3241dUMP By similarity
Binding site4701dUMP By similarity
Binding site5001dUMP By similarity

Natural variations

Natural variant1101S → N in pyrimethamine resistance.
Natural variant1771S → F in pyrimethamine resistance.

Sequences

Sequence LengthMass (Da)Tools
Q27713 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 6E638C2B02FEC13A

FASTA58768,932
        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

« Hide

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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 12-201.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		U12275 Genomic DNA. Translation: AAB60237.1.
L28119 Genomic DNA. Translation: AAA29581.1.

3D structure databases

ProteinModelPortalQ27713.
SMRQ27713. Positions 1-238, 264-587.
ModBaseSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Phylogenomic databases

HOGENOMHOG000257901.

Enzyme and pathway databases

UniPathwayUPA00077; UER00158.

Family and domain databases

Gene3D3.30.572.10. 1 hit.
3.40.430.10. 1 hit.
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. Thymidylat_synth_C. 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

ChEMBLCHEMBL3963.
DrugBankDB00440. Trimethoprim.

Entry information

Entry nameDRTS_PLABA
AccessionPrimary (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: April 3, 2013
This is version 74 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)

Relevant documents

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

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