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P07382

- DRTS_LEIMA

UniProt

P07382 - DRTS_LEIMA

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
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    • History
      Entry version 103 (01 Oct 2014)
      Sequence version 1 (01 Apr 1988)
      Previous versions | rss
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    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

    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.
    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

    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.
    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

    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 1, 2014
    This is version 103 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