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Protein

Bifunctional dihydrofolate reductase-thymidylate synthase

Gene
N/A
Organism
Plasmodium chabaudi
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
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 sitei165Substrate; via carbonyl oxygenBy similarity1
Binding sitei171SubstrateBy similarity1
Binding sitei186SubstrateBy similarity1
Binding sitei320dUMPBy similarity1
Active sitei465By similarity1
Binding sitei466dUMPBy similarity1
Binding sitei496dUMPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi36 – 42NADPBy similarity7
Nucleotide bindingi104 – 106NADPBy similarity3
Nucleotide bindingi125 – 128NADPBy similarity4
Nucleotide bindingi166 – 173NADPBy similarity8
Nucleotide bindingi484 – 488dUMPBy similarity5
Nucleotide bindingi526 – 528dUMPBy 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 chabaudi
Taxonomic identifieri5825 [NCBI]
Taxonomic lineageiEukaryotaAlveolataApicomplexaAconoidasidaHaemosporidaPlasmodiidaePlasmodiumPlasmodium (Vinckeia)

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001863481 – 583Bifunctional dihydrofolate reductase-thymidylate synthaseAdd BLAST583

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

STRINGi5825.PCHAS_072830.

Structurei

3D structure databases

ProteinModelPortaliP20712.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini9 – 229DHFRAdd BLAST221

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni298 – 583Thymidylate synthaseAdd BLAST286

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

eggNOGiENOG410K5TU. Eukaryota.
KOG0673. Eukaryota.
KOG1324. Eukaryota.
COG0207. LUCA.
COG0262. LUCA.
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.

P20712-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEDISEIFDI YAICACCKVL NSNEKAGCFS NKTFKGLGNE GGLPWKCNSV
60 70 80 90 100
DMKHFSSVTS YVNETNYMRL KWKRDRYMEK NNVKLNTDGI PSVDKLQNIV
110 120 130 140 150
VMGKASWESI PSKFKPLQNR INIILSRTLK KEDLAKEYNN VIIINSVDDL
160 170 180 190 200
FPILKCIKYY KCFIIGGASV YKEFLDRNLI KKIYFTRINN AYTCDVLFPD
210 220 230 240 250
INEDLFKITS ISDVYSSNNT TLDFVIYSKT KEIHEEINPN DELFNNTFLG
260 270 280 290 300
VCDEKNTNFD DEDDYTYFSF NKHKDNIKKN SEHAHHFKIY NSIKYKHHPE
310 320 330 340 350
YQYLNIIYDI IMHGNKQDDR TGVGVLSKFG YMMKFNLSEY FPLLTTKKLF
360 370 380 390 400
VRGIIEELLW FIRGETNGNT LLEKNVRIWE ANGTREFLDN RKLFHREVND
410 420 430 440 450
LGPIYGFQWR HFGAEYTDMH ADYKDKGVDQ LKNIINLIKN DPTCRRIILC
460 470 480 490 500
AWNVKDLDQM ALPPCHILCQ FYVFDGKLSC IMYQRSCDLG LGVPFNIASY
510 520 530 540 550
SIFTYMIAQV CNLQPAEFIH VLGNAHVYNN HVESLKVQLN RTPYPFPTLK
560 570 580
LNPEIKNIED FTISDFTVQN YVHHDKISMD MAA
Length:583
Mass (Da):68,051
Last modified:February 1, 1991 - v1
Checksum:i4AA55E1C987E6FD7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti27G → S in AAB59201 (PubMed:7969277).Curated1
Sequence conflicti156C → S in AAB59201 (PubMed:7969277).Curated1
Sequence conflicti164I → V in AAB59201 (PubMed:7969277).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti106S → I in pyrimethamine resistance. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M30834 Genomic DNA. Translation: AAA29587.1.
L28120 Genomic DNA. Translation: AAB59201.1.
PIRiA33484. RDZQTB.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M30834 Genomic DNA. Translation: AAA29587.1.
L28120 Genomic DNA. Translation: AAB59201.1.
PIRiA33484. RDZQTB.

3D structure databases

ProteinModelPortaliP20712.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi5825.PCHAS_072830.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

eggNOGiENOG410K5TU. Eukaryota.
KOG0673. Eukaryota.
KOG1324. Eukaryota.
COG0207. LUCA.
COG0262. LUCA.
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_PLACH
AccessioniPrimary (citable) accession number: P20712
Secondary accession number(s): Q27715
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: February 1, 1991
Last modified: November 30, 2016
This is version 93 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.