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P07382 (DRTS_LEIMA) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 97. 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
Gene names
ORF Names:LmjF06.0860, LmjF_06_0860
OrganismLeishmania major [Reference proteome]
Taxonomic identifier5664 [NCBI]
Taxonomic lineageEukaryota › Euglenozoa › Kinetoplastida › Trypanosomatidae › Leishmaniinae › Leishmania ›

Protein attributes

Sequence length520 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 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.

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 – 520520Bifunctional dihydrofolate reductase-thymidylate synthase
PRO_0000186345

Regions

Domain26 – 229204DHFR
Nucleotide binding38 – 447NADP By similarity
Nucleotide binding81 – 833NADP By similarity
Nucleotide binding102 – 1054NADP By similarity
Nucleotide binding157 – 1648NADP By similarity
Nucleotide binding421 – 4255dUMP By similarity
Nucleotide binding463 – 4653dUMP By similarity
Region234 – 520287Thymidylate synthase

Sites

Active site4001 By similarity
Binding site301Substrate; via carbonyl oxygen By similarity
Binding site321NADP; via amide nitrogen and carbonyl oxygen By similarity
Binding site521Substrate By similarity
Binding site1621Substrate By similarity
Binding site1801Substrate By similarity
Binding site2541dUMP By similarity
Binding site4011dUMP By similarity
Binding site4331dUMP By similarity

Experimental info

Sequence conflict281S → C in AAA29272. Ref.2
Sequence conflict491V → S in AAA29272. Ref.2
Sequence conflict72 – 765KKRNA → EEAQR in AAA29272. Ref.2
Sequence conflict125 – 1273QDV → RML in AAA29272. Ref.2
Sequence conflict3071A → T in AAA29272. Ref.2
Sequence conflict3971L → V in AAA29272. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P07382 [UniParc].

Last modified April 1, 1988. Version 1.
Checksum: 7D221F2CF2BE43D4

FASTA52058,689
        10         20         30         40         50         60 
MSRAAARFKI PMPETKADFA FPSLRAFSIV VALDMQHGIG DGESIPWRVP EDMTFFKNQT 

        70         80         90        100        110        120 
TLLRNKKPPT EKKRNAVVMG RKTWESVPVK FRPLKGRLNI VLSSKATVEE LLAPLPEGQR 

       130        140        150        160        170        180 
AAAAQDVVVV NGGLAEALRL LARPLYCSSI ETAYCVGGAQ VYADAMLSPC IEKLQEVYLT 

       190        200        210        220        230        240 
RIYATAPACT RFFPFPPENA ATAWDLASSQ GRRKSEAEGL EFEICKYVPR NHEERQYLEL 

       250        260        270        280        290        300 
IDRIMKTGIV KEDRTGVGTI SLFGAQMRFS LRDNRLPLLT TKRVFWRGVC EELLWFLRGE 

       310        320        330        340        350        360 
TSAQLLADKD IHIWDGNGSR EFLDSRGLTE NKEMDLGPVY GFQWRHFGAD YKGFEANYDG 

       370        380        390        400        410        420 
EGVDQIKLIV ETIKTNPNDR RLLVTAWNPC ALQKMALPPC HLLAQFYVNT DTSELSCMLY 

       430        440        450        460        470        480 
QRSCDMGLGV PFNIASYALL TILIAKATGL RPGELVHTLG DAHVYRNHVD ALKAQLERVP 

       490        500        510        520 
HAFPTLIFKE ERQYLEDYEL TDMEVIDYVP HPAIKMEMAV

« Hide

References

« Hide 'large scale' references
[1]"Primary structure of the gene encoding the bifunctional dihydrofolate reductase-thymidylate synthase of Leishmania major."
Beverley S.M., Ellenberger T.E., Cordingley J.S.
Proc. Natl. Acad. Sci. U.S.A. 83:2584-2588(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Bifunctional thymidylate synthase-dihydrofolate reductase from Leishmania tropica: sequence homology with the corresponding monofunctional proteins."
Grumont R., Washtien W.L., Caput D., Santi D.V.
Proc. Natl. Acad. Sci. U.S.A. 83:5387-5391(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]Kapler G.M., Zhang K., Beverley S.
Submitted (FEB-1990) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: LT25Z.
[4]"The genome of the kinetoplastid parasite, Leishmania major."
Ivens A.C., Peacock C.S., Worthey E.A., Murphy L., Aggarwal G., Berriman M., Sisk E., Rajandream M.A., Adlem E., Aert R., Anupama A., Apostolou Z., Attipoe P., Bason N., Bauser C., Beck A., Beverley S.M., Bianchettin G. expand/collapse author list , Borzym K., Bothe G., Bruschi C.V., Collins M., Cadag E., Ciarloni L., Clayton C., Coulson R.M.R., Cronin A., Cruz A.K., Davies R.M., De Gaudenzi J., Dobson D.E., Duesterhoeft A., Fazelina G., Fosker N., Frasch A.C., Fraser A., Fuchs M., Gabel C., Goble A., Goffeau A., Harris D., Hertz-Fowler C., Hilbert H., Horn D., Huang Y., Klages S., Knights A., Kube M., Larke N., Litvin L., Lord A., Louie T., Marra M., Masuy D., Matthews K., Michaeli S., Mottram J.C., Mueller-Auer S., Munden H., Nelson S., Norbertczak H., Oliver K., O'neil S., Pentony M., Pohl T.M., Price C., Purnelle B., Quail M.A., Rabbinowitsch E., Reinhardt R., Rieger M., Rinta J., Robben J., Robertson L., Ruiz J.C., Rutter S., Saunders D., Schaefer M., Schein J., Schwartz D.C., Seeger K., Seyler A., Sharp S., Shin H., Sivam D., Squares R., Squares S., Tosato V., Vogt C., Volckaert G., Wambutt R., Warren T., Wedler H., Woodward J., Zhou S., Zimmermann W., Smith D.F., Blackwell J.M., Stuart K.D., Barrell B.G., Myler P.J.
Science 309:436-442(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: MHOM/IL/81/Friedlin.
[5]"Limited proteolysis of the bifunctional thymidylate synthase-dihydrofolate reductase from Leishmania tropica."
Garvey E.P., Santi D.V.
Proc. Natl. Acad. Sci. U.S.A. 82:7188-7192(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 334-361.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		M12734 Genomic DNA. Translation: AAA29232.1.
M14330 Genomic DNA. Translation: AAA29272.1.
X51733 Genomic DNA. Translation: CAA36019.1.
FR796402 Genomic DNA. Translation: CAJ02132.1.
PIRRDLNTS. A23403.
RefSeqXP_001680857.1. XM_001680805.1.

3D structure databases

ProteinModelPortalP07382.
SMRP07382. Positions 8-514.
ModBaseSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblProtistsLmjF.06.0860:mRNA; LmjF.06.0860:pep; LmjF.06.0860.
GeneID5649109.
KEGGlma:LMJF_06_0860.

Phylogenomic databases

HOGENOMHOG000257901.
KOK13998.
OMACEAVHLT.
ProtClustDBPTZ00164.

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

BindingDBP07382.
ChEMBLCHEMBL4614.

Entry information

Entry nameDRTS_LEIMA
AccessionPrimary (citable) accession number: P07382
Secondary accession number(s): Q4QIZ1
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: April 1, 1988
Last modified: April 3, 2013
This is version 97 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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