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Protein

Bifunctional dihydrofolate reductase-thymidylate synthase

Gene
N/A
Organism
Plasmodium vivax
Status
Reviewed-Annotation score: -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.

Catalytic activityi

5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH.1 Publication
5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP.1 Publication

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 (DHFR-TS), Bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS), Bifunctional dihydrofolate reductase-thymidylate synthase (PVC01_050029000), Bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS), Bifunctional dihydrofolate reductase-thymidylate synthase, Bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS), Bifunctional dihydrofolate reductase-thymidylate synthase (PVT01_050029600), Bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS), Bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS), Bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS), Bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS), Bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS), Bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS), Bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS), Bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS), Bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS), Bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS), Bifunctional dihydrofolate reductase-thymidylate synthase (PVP01_0526600)
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 sitei15NADP; via amide nitrogen and carbonyl oxygen1
Binding sitei53Substrate1
Binding sitei153NADP; via carbonyl oxygen1
Binding sitei173Substrate; via carbonyl oxygen1
Binding sitei179Substrate1
Binding sitei194Substrate1
Binding sitei360dUMPBy similarity1
Active sitei505By similarity1
Binding sitei506dUMPBy similarity1
Binding sitei536dUMPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi38 – 44NADP7
Nucleotide bindingi115 – 117NADP3
Nucleotide bindingi137 – 139NADP3
Nucleotide bindingi174 – 181NADP8
Nucleotide bindingi524 – 528dUMPBy similarity5
Nucleotide bindingi566 – 568dUMPBy similarity3

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionMethyltransferase, Multifunctional enzyme, Oxidoreductase, Transferase
Biological processNucleotide biosynthesis, One-carbon metabolism
LigandNADP

Enzyme and pathway databases

BRENDAi1.5.1.3 4894
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 vivax
Taxonomic identifieri5855 [NCBI]
Taxonomic lineageiEukaryotaAlveolataApicomplexaAconoidasidaHaemosporidaPlasmodiidaePlasmodiumPlasmodium (Plasmodium)

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001863511 – 623Bifunctional dihydrofolate reductase-thymidylate synthaseAdd BLAST623

Proteomic databases

PRIDEiO02604

Interactioni

Subunit structurei

Homodimer.1 Publication

Chemistry databases

BindingDBiO02604

Structurei

Secondary structure

1623
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi4 – 7Combined sources4
Beta strandi10 – 19Combined sources10
Beta strandi23 – 26Combined sources4
Beta strandi38 – 41Combined sources4
Beta strandi46 – 48Combined sources3
Helixi51 – 62Combined sources12
Helixi66 – 68Combined sources3
Helixi69 – 83Combined sources15
Beta strandi109 – 114Combined sources6
Helixi115 – 119Combined sources5
Helixi123 – 125Combined sources3
Beta strandi131 – 136Combined sources6
Turni142 – 144Combined sources3
Beta strandi150 – 153Combined sources4
Helixi155 – 163Combined sources9
Beta strandi170 – 174Combined sources5
Helixi176 – 184Combined sources9
Beta strandi189 – 200Combined sources12
Beta strandi203 – 205Combined sources3
Helixi211 – 213Combined sources3
Beta strandi214 – 219Combined sources6
Beta strandi223 – 225Combined sources3
Beta strandi228 – 237Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2BL9X-ray1.90A4-238[»]
2BLAX-ray2.50A4-238[»]
2BLBX-ray3.00A4-238[»]
2BLCX-ray2.25A4-238[»]
ProteinModelPortaliO02604
SMRiO02604
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO02604

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini9 – 237DHFRAdd BLAST229
Repeati88 – 9114
Repeati94 – 9724
Repeati100 – 10334

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni13 – 14Substrate binding2
Regioni88 – 1033 X 4 AA repeats of G-G-D-NAdd BLAST16
Regioni337 – 623Thymidylate synthaseAdd BLAST287

Domaini

The repeat region is missing in the pyrimethamine-resistant isolates BUR-98 and BUR-151.

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

Keywords - Domaini

Repeat

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
InterProiView protein in InterPro
IPR024072 DHFR-like_dom_sf
IPR012262 DHFR-TS
IPR017925 DHFR_CS
IPR001796 DHFR_dom
IPR023451 Thymidate_synth/dCMP_Mease
IPR036926 Thymidate_synth/dCMP_Mease_sf
IPR000398 Thymidylate_synthase
IPR020940 Thymidylate_synthase_AS
PANTHERiPTHR11548:SF7 PTHR11548:SF7, 3 hits
PfamiView protein in Pfam
PF00186 DHFR_1, 1 hit
PF00303 Thymidylat_synt, 1 hit
PIRSFiPIRSF000389 DHFR-TS, 1 hit
PRINTSiPR00108 THYMDSNTHASE
SUPFAMiSSF53597 SSF53597, 1 hit
SSF55831 SSF55831, 1 hit
TIGRFAMsiTIGR03284 thym_sym, 1 hit
PROSITEiView protein in PROSITE
PS00075 DHFR_1, 1 hit
PS51330 DHFR_2, 1 hit
PS00091 THYMIDYLATE_SYNTHASE, 1 hit

Sequencei

Sequence statusi: Complete.

O02604-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEDLSDVFDI YAICACCKVA PTSEGTKNEP FSPRTFRGLG NKGTLPWKCN
60 70 80 90 100
SVDMKYFSSV TTYVDESKYE KLKWKRERYL RMEASQGGGD NTSGGDNTHG
110 120 130 140 150
GDNADKLQNV VVMGRSSWES IPKQYKPLPN RINVVLSKTL TKEDVKEKVF
160 170 180 190 200
IIDSIDDLLL LLKKLKYYKC FIIGGAQVYR ECLSRNLIKQ IYFTRINGAY
210 220 230 240 250
PCDVFFPEFD ESQFRVTSVS EVYNSKGTTL DFLVYSKVGG GVDGGASNGS
260 270 280 290 300
TATALRRTAM RSTAMRRNVA PRTAAPPMGP HSRANGERAP PRARARRTTP
310 320 330 340 350
RQRKTTSCTS ALTTKWGRKT RSTCKILKFT TASRLMQHPE YQYLGIIYDI
360 370 380 390 400
IMNGNKQGDR TGVGVMSNFG YMMKFNLSEY FPLLTTKKLF LRGIIEELLW
410 420 430 440 450
FIRGETNGNT LLNKNVRIWE ANGTREFLDN RKLFHREVND LGPIYGFQWR
460 470 480 490 500
HFGAEYTNMH DNYEDKGVDQ LKNVIHLIKN EPTSRRIILC AWNVKDLDQM
510 520 530 540 550
ALPPCHILCQ FYVFDGKLSC IMYQRSCDLG LGVPFNIASY SIFTHMIAQV
560 570 580 590 600
CNLQPAQFIH ILGNAHVYNN HVDSLKVQLN RIPYPFPTLK LNPEVKNIED
610 620
FTISDFTIEN YVHHDKITME MAA
Length:623
Mass (Da):71,057
Last modified:May 30, 2000 - v2
Checksum:i3E6E958F04FB5828
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti58S → R in the pyrimethamine-resistant isolates BUR-98 and BUR-151; interferes with inhibitor binding. 1
Natural varianti117S → N in the pyrimethamine-resistant isolates BUR-98 and BUR-151. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X98123 Genomic DNA Translation: CAA66805.1
PIRiJC6568

Similar proteinsi

Entry informationi

Entry nameiDRTS_PLAVI
AccessioniPrimary (citable) accession number: O02604
Secondary accession number(s): O15873
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 30, 2000
Last modified: May 23, 2018
This is version 104 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)

Miscellaneousi

Keywords - Technical termi

3D-structure

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