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P07382

- DRTS_LEIMA

UniProt

P07382 - DRTS_LEIMA

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Protein

Bifunctional dihydrofolate reductase-thymidylate synthase

Gene
LmjF06.0860, LmjF_06_0860
Organism
Leishmania major
Status
Reviewed - Annotation score: 4 out of 5 - Experimental evidence at protein leveli

Functioni

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.UniRule annotation

Catalytic activityi

5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH.UniRule annotation
5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP.UniRule annotation

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei30 – 301Substrate; via carbonyl oxygen By similarity
Binding sitei32 – 321NADP; via amide nitrogen and carbonyl oxygen By similarity
Binding sitei52 – 521Substrate By similarity
Binding sitei162 – 1621Substrate By similarity
Binding sitei180 – 1801Substrate By similarity
Binding sitei254 – 2541dUMP By similarity
Active sitei400 – 4001 By similarity
Binding sitei401 – 4011dUMP By similarity
Binding sitei433 – 4331dUMP By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi38 – 447NADP By similarity
Nucleotide bindingi81 – 833NADP By similarity
Nucleotide bindingi102 – 1054NADP By similarity
Nucleotide bindingi157 – 1648NADP By similarity
Nucleotide bindingi421 – 4255dUMP By similarity
Nucleotide bindingi463 – 4653dUMP By similarity

GO - Molecular functioni

  1. dihydrofolate reductase activity Source: UniProtKB-EC
  2. thymidylate synthase activity Source: UniProtKB-EC

GO - Biological processi

  1. dTMP biosynthetic process Source: InterPro
  2. glycine biosynthetic process Source: InterPro
  3. one-carbon metabolic process Source: UniProtKB-KW
  4. tetrahydrofolate biosynthetic process Source: UniProtKB-UniPathway
Complete GO annotation...

Keywords - Molecular functioni

Methyltransferase, Oxidoreductase, Transferase

Keywords - Biological processi

Nucleotide biosynthesis, One-carbon metabolism

Keywords - Ligandi

NADP

Enzyme and pathway databases

UniPathwayiUPA00077; UER00158.

Names & Taxonomyi

Protein namesi
Recommended name:
Bifunctional dihydrofolate reductase-thymidylate synthase
Short name:
DHFR-TS
Including the following 2 domains:
Dihydrofolate reductase (EC:1.5.1.3)
Thymidylate synthase (EC:2.1.1.45)
Gene namesi
ORF Names:LmjF06.0860, LmjF_06_0860
OrganismiLeishmania major
Taxonomic identifieri5664 [NCBI]
Taxonomic lineageiEukaryotaEuglenozoaKinetoplastidaTrypanosomatidaeLeishmaniinaeLeishmania
ProteomesiUP000000542: Chromosome 6

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 520520Bifunctional dihydrofolate reductase-thymidylate synthaseUniRule annotationPRO_0000186345Add
BLAST

Interactioni

Structurei

3D structure databases

ProteinModelPortaliP07382.
SMRiP07382. Positions 8-514.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini26 – 229204DHFRAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni234 – 520287Thymidylate synthaseUniRule annotationAdd
BLAST

Sequence similaritiesi

In the N-terminal section; belongs to the dihydrofolate reductase family.
In the C-terminal section; belongs to the thymidylate synthase family.

Phylogenomic databases

HOGENOMiHOG000257901.
KOiK13998.
OMAiLTCMIAQ.

Family and domain databases

Gene3Di3.30.572.10. 1 hit.
3.40.430.10. 1 hit.
HAMAPiMF_00008. Thymidy_synth_bact.
InterProiIPR024072. 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]
PfamiPF00186. DHFR_1. 1 hit.
PF00303. Thymidylat_synt. 1 hit.
[Graphical view]
PIRSFiPIRSF000389. DHFR-TS. 1 hit.
PRINTSiPR00108. THYMDSNTHASE.
SUPFAMiSSF53597. SSF53597. 1 hit.
SSF55831. SSF55831. 1 hit.
TIGRFAMsiTIGR03284. thym_sym. 1 hit.
PROSITEiPS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
PS00091. THYMIDYLATE_SYNTHASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P07382-1 [UniParc]FASTAAdd to Basket

« Hide

MSRAAARFKI PMPETKADFA FPSLRAFSIV VALDMQHGIG DGESIPWRVP    50
EDMTFFKNQT TLLRNKKPPT EKKRNAVVMG RKTWESVPVK FRPLKGRLNI 100
VLSSKATVEE LLAPLPEGQR AAAAQDVVVV NGGLAEALRL LARPLYCSSI 150
ETAYCVGGAQ VYADAMLSPC IEKLQEVYLT RIYATAPACT RFFPFPPENA 200
ATAWDLASSQ GRRKSEAEGL EFEICKYVPR NHEERQYLEL IDRIMKTGIV 250
KEDRTGVGTI SLFGAQMRFS LRDNRLPLLT TKRVFWRGVC EELLWFLRGE 300
TSAQLLADKD IHIWDGNGSR EFLDSRGLTE NKEMDLGPVY GFQWRHFGAD 350
YKGFEANYDG EGVDQIKLIV ETIKTNPNDR RLLVTAWNPC ALQKMALPPC 400
HLLAQFYVNT DTSELSCMLY QRSCDMGLGV PFNIASYALL TILIAKATGL 450
RPGELVHTLG DAHVYRNHVD ALKAQLERVP HAFPTLIFKE ERQYLEDYEL 500
TDMEVIDYVP HPAIKMEMAV 520
Length:520
Mass (Da):58,689
Last modified:April 1, 1988 - v1
Checksum:i7D221F2CF2BE43D4
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti28 – 281S → C in AAA29272. 1 Publication
Sequence conflicti49 – 491V → S in AAA29272. 1 Publication
Sequence conflicti72 – 765KKRNA → EEAQR in AAA29272. 1 Publication
Sequence conflicti125 – 1273QDV → RML in AAA29272. 1 Publication
Sequence conflicti307 – 3071A → T in AAA29272. 1 Publication
Sequence conflicti397 – 3971L → V in AAA29272. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M12734 Genomic DNA. Translation: AAA29232.1.
M14330 Genomic DNA. Translation: AAA29272.1.
X51733 Genomic DNA. Translation: CAA36019.1.
FR796402 Genomic DNA. Translation: CAJ02132.1.
PIRiA23403. RDLNTS.
RefSeqiXP_001680857.1. XM_001680805.1.

Genome annotation databases

GeneIDi5649109.
KEGGilma:LMJF_06_0860.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M12734 Genomic DNA. Translation: AAA29232.1 .
M14330 Genomic DNA. Translation: AAA29272.1 .
X51733 Genomic DNA. Translation: CAA36019.1 .
FR796402 Genomic DNA. Translation: CAJ02132.1 .
PIRi A23403. RDLNTS.
RefSeqi XP_001680857.1. XM_001680805.1.

3D structure databases

ProteinModelPortali P07382.
SMRi P07382. Positions 8-514.
ModBasei Search...
MobiDBi Search...

Chemistry

BindingDBi P07382.
ChEMBLi CHEMBL4614.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 5649109.
KEGGi lma:LMJF_06_0860.

Phylogenomic databases

HOGENOMi HOG000257901.
KOi K13998.
OMAi LTCMIAQ.

Enzyme and pathway databases

UniPathwayi UPA00077 ; UER00158 .

Family and domain databases

Gene3Di 3.30.572.10. 1 hit.
3.40.430.10. 1 hit.
HAMAPi MF_00008. Thymidy_synth_bact.
InterProi IPR024072. 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 ]
Pfami PF00186. DHFR_1. 1 hit.
PF00303. Thymidylat_synt. 1 hit.
[Graphical view ]
PIRSFi PIRSF000389. DHFR-TS. 1 hit.
PRINTSi PR00108. THYMDSNTHASE.
SUPFAMi SSF53597. SSF53597. 1 hit.
SSF55831. SSF55831. 1 hit.
TIGRFAMsi TIGR03284. thym_sym. 1 hit.
PROSITEi PS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
PS00091. THYMIDYLATE_SYNTHASE. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.

Entry informationi

Entry nameiDRTS_LEIMA
AccessioniPrimary (citable) accession number: P07382
Secondary accession number(s): Q4QIZ1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: April 1, 1988
Last modified: June 11, 2014
This is version 102 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Multifunctional enzyme, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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