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Protein

Bifunctional dihydrofolate reductase-thymidylate synthase

Gene
N/A
Organism
Plasmodium berghei (strain Anka)
Status
Reviewed-Annotation score: 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: 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, Bifunctional dihydrofolate reductase-thymidylate synthase (PB000415.02.0), Bifunctional dihydrofolate reductase-thymidylate synthase (PBANKA_071930)
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 sitei51SubstrateBy similarity1
Binding sitei173Substrate; via carbonyl oxygenBy similarity1
Binding sitei179SubstrateBy similarity1
Binding sitei194SubstrateBy similarity1
Binding sitei324dUMPBy similarity1
Active sitei469By similarity1
Binding sitei470dUMPBy similarity1
Binding sitei500dUMPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi36 – 42NADPBy similarity7
Nucleotide bindingi108 – 110NADPBy similarity3
Nucleotide bindingi129 – 132NADPBy similarity4
Nucleotide bindingi174 – 181NADPBy similarity8
Nucleotide bindingi488 – 492dUMPBy similarity5
Nucleotide bindingi530 – 532dUMPBy 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.

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)
OrganismiPlasmodium berghei (strain Anka)
Taxonomic identifieri5823 [NCBI]
Taxonomic lineageiEukaryotaAlveolataApicomplexaAconoidasidaHaemosporidaPlasmodiidaePlasmodiumPlasmodium (Vinckeia)

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3963.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001863471 – 587Bifunctional dihydrofolate reductase-thymidylate synthaseAdd BLAST587

Interactioni

Subunit structurei

Homodimer.By similarity

Chemistry databases

BindingDBiQ27713.

Structurei

3D structure databases

ProteinModelPortaliQ27713.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini9 – 237DHFRAdd BLAST229

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni301 – 587Thymidylate synthaseAdd BLAST287

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.

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.

Q27713-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEDLSETFDI YAICACCKVL NDDEKVRCFN NKTFKGIGNA GVLPWKCNLI
60 70 80 90 100
DMKYFSSVTS YINENNYIRL KWKRDKYMEK HNLKNNVELN TNIISSTNNL
110 120 130 140 150
QNIVVMGKKS WESIPKKFKP LQNRINIILS RTLKKEDIVN ENNNENNNVI
160 170 180 190 200
IIKSVDDLFP ILKCTKYYKC FIIGGSSVYK EFLDRNLIKK IYFTRINNSY
210 220 230 240 250
NCDVLFPEIN ENLFKITSIS DVYYSNNTTL DFIIYSKTKE INPNEEVPNN
260 270 280 290 300
TFLGVCDEQN KAFDDEDDYT YFSFNKNKEN IKKNSEHAHN FKIYNSIKYK
310 320 330 340 350
NHPEYQYLNI IYDIIMHGNK QDDRTGVGVL SKFGYMMKFN LNEYFPLLTT
360 370 380 390 400
KKLFIRGIIE ELLWFIRGET NGNTLLEKNV RIWEANGTRE FLDNRKLFHR
410 420 430 440 450
EVNDLGPIYG FQWRHFGAEY TDMHDNYKDK GVDQLKNIIN LIKNDPTCRR
460 470 480 490 500
IILCAWNVKN LDQMALPPCH ILCQFYVFDG KLSCIMYQRS CDLGLGVPFN
510 520 530 540 550
IASYSIFTYM IAQVCNLQAA EFIHVLGNAH VYNNHIESLK IQLNRTPYPF
560 570 580
PTLKLNPDIK NIEDFTISDF TVQNYVHHDK INMDMAA
Length:587
Mass (Da):68,932
Last modified:November 1, 1996 - v1
Checksum:i6E638C2B02FEC13A
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti110S → N in pyrimethamine resistance. 1
Natural varianti177S → F in pyrimethamine resistance. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U12275 Genomic DNA. Translation: AAB60237.1.
L28119 Genomic DNA. Translation: AAA29581.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U12275 Genomic DNA. Translation: AAB60237.1.
L28119 Genomic DNA. Translation: AAA29581.1.

3D structure databases

ProteinModelPortaliQ27713.
ModBaseiSearch...
MobiDBiSearch...

Chemistry databases

BindingDBiQ27713.
ChEMBLiCHEMBL3963.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

HOGENOMiHOG000257901.

Enzyme and pathway databases

UniPathwayiUPA00077; UER00158.

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_PLABA
AccessioniPrimary (citable) accession number: Q27713
Secondary accession number(s): Q27714
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: November 30, 2016
This is version 88 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

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.