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P16126

- DRTS_LEIAM

UniProt

P16126 - DRTS_LEIAM

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Protein

Bifunctional dihydrofolate reductase-thymidylate synthase

Gene
N/A
Organism
Leishmania amazonensis
Status
Reviewed - Annotation score: 4 out of 5- Protein inferred from homologyi

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)
OrganismiLeishmania amazonensis
Taxonomic identifieri5659 [NCBI]
Taxonomic lineageiEukaryotaEuglenozoaKinetoplastidaTrypanosomatidaeLeishmaniinaeLeishmania

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 520520Bifunctional dihydrofolate reductase-thymidylate synthasePRO_0000186344Add
BLAST

Structurei

3D structure databases

ProteinModelPortaliP16126.
SMRiP16126. 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

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.

P16126-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MSRAAAKFKI PMPVTKADFA FPSLRAFSIV VALDKQHGIG DGESIPWRVP
60 70 80 90 100
EDMAFFKDQT TLLRNKKPPT DKKRNAVVMG RKTWESVPVK FRPLKGRLNV
110 120 130 140 150
VLSSKATVEE LLAPLPEEKR AAAAQDIVVV NGGLAAAVRL LARPPYCSSI
160 170 180 190 200
ETAYCVGGAQ VYADAMLSPC VEKLQEVYLT RIHTTAPACT RFFPFPPENA
210 220 230 240 250
ATAWDLASSQ GRRKSAVDGL EFEICKYVPR NHEERQYLEL IDRIMKTGIA
260 270 280 290 300
KEDRTGVGTL SLFGAQMRFS LRDNRLPLLT TKRVFWRGVC EELLWFLRGE
310 320 330 340 350
TNAQLLADKD IHIWDGNGSR EFLDSRGLTE NTEMDLGPVY GFQWRHFGAE
360 370 380 390 400
YRGLEANYDG EGVDQIKFIV ETIKANPNDR RLLFTAWNPC ALHKMALPPC
410 420 430 440 450
HLLAQFYVNT EKSELSCMLY QRSCDMGLGV PFNIASYALL TILIAKATGL
460 470 480 490 500
RPGELVHTLG DAHVYRSHID ALKAQLERVP HAFPTLVFKE ERQFLEDYEL
510 520
MDMEVIDYVP HPPIKMEMAV
Length:520
Mass (Da):58,610
Last modified:April 1, 1990 - v1
Checksum:iB59CEE0CC3CF7BED
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X51735 Genomic DNA. Translation: CAA36020.1.
PIRiS15756. RDLNTZ.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X51735 Genomic DNA. Translation: CAA36020.1 .
PIRi S15756. RDLNTZ.

3D structure databases

ProteinModelPortali P16126.
SMRi P16126. Positions 8-514.
ModBasei Search...
MobiDBi Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

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. "Sequence of the dihydrofolate reductase-thymidylate synthase (DHFR-TS) gene of Leishmania amazonensis."
    Nelson K., Alonso G., Langer P.J., Beverley S.M.
    Nucleic Acids Res. 18:2819-2819(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: MHOM/BR/77/LTB0016/C1S1.

Entry informationi

Entry nameiDRTS_LEIAM
AccessioniPrimary (citable) accession number: P16126
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: October 1, 2014
This is version 84 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)

Miscellaneousi

Keywords - Technical termi

Multifunctional enzyme

Documents

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

External Data

Dasty 3