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P07382

- DRTS_LEIMA

UniProt

P07382 - DRTS_LEIMA

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Protein

Bifunctional dihydrofolate reductase-thymidylate synthase

Gene

LmjF06.0860

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).By similarity

Catalytic activityi

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

Pathwayi

Sites

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

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi38 – 447NADPBy similarity
Nucleotide bindingi81 – 833NADPBy similarity
Nucleotide bindingi102 – 1054NADPBy similarity
Nucleotide bindingi157 – 1648NADPBy similarity
Nucleotide bindingi421 – 4255dUMPBy similarity
Nucleotide bindingi463 – 4653dUMPBy 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 synthasePRO_0000186345Add
BLAST

Interactioni

Structurei

3D structure databases

ProteinModelPortaliP07382.
SMRiP07382. Positions 8-514.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

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

Region

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

Sequence similaritiesi

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

Phylogenomic databases

HOGENOMiHOG000257901.
InParanoidiP07382.
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

        10         20         30         40         50
MSRAAARFKI PMPETKADFA FPSLRAFSIV VALDMQHGIG DGESIPWRVP
60 70 80 90 100
EDMTFFKNQT TLLRNKKPPT EKKRNAVVMG RKTWESVPVK FRPLKGRLNI
110 120 130 140 150
VLSSKATVEE LLAPLPEGQR AAAAQDVVVV NGGLAEALRL LARPLYCSSI
160 170 180 190 200
ETAYCVGGAQ VYADAMLSPC IEKLQEVYLT RIYATAPACT RFFPFPPENA
210 220 230 240 250
ATAWDLASSQ GRRKSEAEGL EFEICKYVPR NHEERQYLEL IDRIMKTGIV
260 270 280 290 300
KEDRTGVGTI SLFGAQMRFS LRDNRLPLLT TKRVFWRGVC EELLWFLRGE
310 320 330 340 350
TSAQLLADKD IHIWDGNGSR EFLDSRGLTE NKEMDLGPVY GFQWRHFGAD
360 370 380 390 400
YKGFEANYDG EGVDQIKLIV ETIKTNPNDR RLLVTAWNPC ALQKMALPPC
410 420 430 440 450
HLLAQFYVNT DTSELSCMLY QRSCDMGLGV PFNIASYALL TILIAKATGL
460 470 480 490 500
RPGELVHTLG DAHVYRNHVD ALKAQLERVP HAFPTLIFKE ERQYLEDYEL
510 520
TDMEVIDYVP HPAIKMEMAV
Length:520
Mass (Da):58,689
Last modified:April 1, 1988 - v1
Checksum:i7D221F2CF2BE43D4
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti28 – 281S → C in AAA29272. (PubMed:3461439)Curated
Sequence conflicti49 – 491V → S in AAA29272. (PubMed:3461439)Curated
Sequence conflicti72 – 765KKRNA → EEAQR in AAA29272. (PubMed:3461439)Curated
Sequence conflicti125 – 1273QDV → RML in AAA29272. (PubMed:3461439)Curated
Sequence conflicti307 – 3071A → T in AAA29272. (PubMed:3461439)Curated
Sequence conflicti397 – 3971L → V in AAA29272. (PubMed:3461439)Curated

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.
InParanoidi P07382.
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: October 29, 2014
This is version 104 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