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Protein

Bifunctional dihydrofolate reductase-thymidylate synthase

Gene
N/A
Organism
Trypanosoma brucei brucei
Status
Reviewed-Annotation score: 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

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

Pathwayi: dTTP biosynthesis

This protein is involved in the pathway dTTP biosynthesis, which is part of Pyrimidine metabolism.
View all proteins of this organism that are known to be involved in the pathway dTTP biosynthesis and in Pyrimidine metabolism.

Pathwayi: tetrahydrofolate biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate.
Proteins known to be involved in this subpathway in this organism are:
  1. Bifunctional dihydrofolate reductase-thymidylate synthase
This subpathway is part of the pathway tetrahydrofolate biosynthesis, which is itself part of Cofactor biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate, the pathway tetrahydrofolate biosynthesis and in Cofactor biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei32Substrate; via carbonyl oxygenBy similarity1
Binding sitei34NADP; via amide nitrogen and carbonyl oxygenBy similarity1
Binding sitei54SubstrateBy similarity1
Binding sitei160Substrate; via carbonyl oxygenBy similarity1
Binding sitei166SubstrateBy similarity1
Binding sitei184SubstrateBy similarity1
Binding sitei263dUMPBy similarity1
Active sitei409By similarity1
Binding sitei410dUMPBy similarity1
Binding sitei440dUMPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi40 – 46NADPBy similarity7
Nucleotide bindingi84 – 86NADPBy similarity3
Nucleotide bindingi105 – 108NADPBy similarity4
Nucleotide bindingi161 – 168NADPBy similarity8
Nucleotide bindingi428 – 432dUMPBy similarity5
Nucleotide bindingi470 – 472dUMPBy similarity3

GO - Molecular functioni

GO - Biological processi

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.
UPA00575.

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)
OrganismiTrypanosoma brucei brucei
Taxonomic identifieri5702 [NCBI]
Taxonomic lineageiEukaryotaEuglenozoaKinetoplastidaTrypanosomatidaeTrypanosoma

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001863531 – 527Bifunctional dihydrofolate reductase-thymidylate synthaseAdd BLAST527

Proteomic databases

PRIDEiQ27783.

Interactioni

Subunit structurei

Homodimer.By similarity

Structurei

Secondary structure

1527
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi29 – 36Combined sources8
Beta strandi40 – 46Combined sources7
Helixi52 – 63Combined sources12
Beta strandi66 – 69Combined sources4
Beta strandi76 – 83Combined sources8
Helixi84 – 89Combined sources6
Helixi92 – 94Combined sources3
Beta strandi100 – 105Combined sources6
Helixi111 – 115Combined sources5
Helixi121 – 127Combined sources7
Helixi128 – 130Combined sources3
Beta strandi131 – 136Combined sources6
Helixi138 – 144Combined sources7
Helixi148 – 153Combined sources6
Beta strandi154 – 159Combined sources6
Helixi163 – 169Combined sources7
Helixi174 – 177Combined sources4
Beta strandi178 – 188Combined sources11
Beta strandi212 – 217Combined sources6
Beta strandi230 – 238Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3QFXX-ray2.20A/B1-241[»]
3RG9X-ray2.00A/B1-240[»]
ProteinModelPortaliQ27783.
SMRiQ27783.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ27783.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini28 – 238DHFRAdd BLAST211

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni243 – 527Thymidylate synthaseAdd BLAST285

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

CDDicd00209. DHFR. 1 hit.
cd00351. TS_Pyrimidine_HMase. 1 hit.
Gene3Di3.30.572.10. 1 hit.
3.40.430.10. 1 hit.
HAMAPiMF_00008. Thymidy_synth_bact. 1 hit.
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.

Q27783-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLSLTRILRK KIPVHELAGK ISRPPLRPFS VVVASDEKGG IGDGGTIPWE
60 70 80 90 100
IPEDMQYFRR VTTNLRGKNV KPSPSKRNAV VMGRKTWDSL PPKFRPLSNR
110 120 130 140 150
LNVVLSRSAT KEQLLAGIPD PIKRAEAAND VVAVNGGLED ALRMLVSKEH
160 170 180 190 200
TSSIETVFCI GGGTIYKQAL CAPCVNVLQA IHRTVVRPAS NSCSVFFDIP
210 220 230 240 250
AAGTKTPEGL ELVRESITDE RVSTGAGGKK YQFEKLVPRN SEEEQYLNLV
260 270 280 290 300
GRIIDEGCTK CDRTGVGTRS LFGAQMRFSL RNNRLPLLTT KRVFWRGVCE
310 320 330 340 350
ELLWFLRGET NAKLLSDKGI HIWDGNGSRA FLDSRGLTDY DEMDLGPVYG
360 370 380 390 400
FQWRHFGADY ISCKVDSEGK GVDQIANIVK SLIENPDDRR MICTAWNPAA
410 420 430 440 450
LPRMALPPCH MMAQFYVSNG ELSCMLYQRS CDMGLGVPFN IASYALLTFL
460 470 480 490 500
MAKASGLRPG ELVHTLGDAH VYSNHVEPCR KQLKRVPRPF PFIVFKQDKE
510 520
FLEDFQESDI EVIDYSPYPV ISMEMAV
Length:527
Mass (Da):58,805
Last modified:November 1, 1996 - v1
Checksum:i39982FC553BF7601
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U20781 Genomic DNA. Translation: AAA91362.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U20781 Genomic DNA. Translation: AAA91362.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3QFXX-ray2.20A/B1-241[»]
3RG9X-ray2.00A/B1-240[»]
ProteinModelPortaliQ27783.
SMRiQ27783.
ModBaseiSearch...
MobiDBiSearch...

Proteomic databases

PRIDEiQ27783.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Enzyme and pathway databases

UniPathwayiUPA00077; UER00158.
UPA00575.

Miscellaneous databases

EvolutionaryTraceiQ27783.

Family and domain databases

CDDicd00209. DHFR. 1 hit.
cd00351. TS_Pyrimidine_HMase. 1 hit.
Gene3Di3.30.572.10. 1 hit.
3.40.430.10. 1 hit.
HAMAPiMF_00008. Thymidy_synth_bact. 1 hit.
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]
ProtoNetiSearch...

Entry informationi

Entry nameiDRTS_TRYBB
AccessioniPrimary (citable) accession number: Q27783
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: November 30, 2016
This is version 91 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)

Miscellaneousi

Keywords - Technical termi

3D-structure, Multifunctional enzyme

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.