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P20712 (DRTS_PLACH) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 83. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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 chabaudi
Taxonomic identifier5825 [NCBI]
Taxonomic lineageEukaryotaAlveolataApicomplexaAconoidasidaHaemosporidaPlasmodiumPlasmodium (Vinckeia)

Protein attributes

Sequence length583 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. HAMAP-Rule MF_00008

Catalytic activity

5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH. HAMAP-Rule MF_00008

5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP. HAMAP-Rule MF_00008

Pathway

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

Subunit structure

Homodimer By similarity. 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 – 583583Bifunctional dihydrofolate reductase-thymidylate synthase HAMAP-Rule MF_00008
PRO_0000186348

Regions

Domain9 – 229221DHFR
Nucleotide binding36 – 427NADP By similarity
Nucleotide binding104 – 1063NADP By similarity
Nucleotide binding125 – 1284NADP By similarity
Nucleotide binding166 – 1738NADP By similarity
Nucleotide binding484 – 4885dUMP By similarity
Nucleotide binding526 – 5283dUMP By similarity
Region298 – 583286Thymidylate synthase HAMAP-Rule MF_00008

Sites

Active site4651 By similarity
Binding site511Substrate By similarity
Binding site1651Substrate; via carbonyl oxygen By similarity
Binding site1711Substrate By similarity
Binding site1861Substrate By similarity
Binding site3201dUMP By similarity
Binding site4661dUMP By similarity
Binding site4961dUMP By similarity

Natural variations

Natural variant1061S → I in pyrimethamine resistance.

Experimental info

Sequence conflict271G → S in AAB59201. Ref.2
Sequence conflict1561C → S in AAB59201. Ref.2
Sequence conflict1641I → V in AAB59201. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P20712 [UniParc].

Last modified February 1, 1991. Version 1.
Checksum: 4AA55E1C987E6FD7

FASTA58368,051
        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 

« Hide

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] [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 12-193.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M30834 Genomic DNA. Translation: AAA29587.1.
L28120 Genomic DNA. Translation: AAB59201.1.
PIRRDZQTB. A33484.

3D structure databases

ProteinModelPortalP20712.
SMRP20712. Positions 1-230, 260-583.
ModBaseSearch...
MobiDBSearch...

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.
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...

Entry information

Entry nameDRTS_PLACH
AccessionPrimary (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: February 19, 2014
This is version 83 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways