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Protein

Bifunctional dihydrofolate reductase-thymidylate synthase

Gene
N/A
Organism
Plasmodium falciparum (isolate K1 / Thailand)
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.

Miscellaneous

K1 is from a pyrimethamine-resistant strain; FCR3 is a pyrimethamine-sensitive strain.

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 sitei16NADP; via amide nitrogen and carbonyl oxygen1
Binding sitei31Substrate; via carbonyl oxygenBy similarity1
Binding sitei54Substrate1
Binding sitei108Substrate1
Binding sitei144NADP; via carbonyl oxygen1
Binding sitei164Substrate; via carbonyl oxygen1
Binding sitei170Substrate1
Binding sitei185SubstrateBy similarity1
Binding sitei345dUMP1
Active sitei490By similarity1
Binding sitei491dUMP1
Binding sitei521dUMP1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi39 – 45NADP7
Nucleotide bindingi106 – 108NADP3
Nucleotide bindingi128 – 130NADP3
Nucleotide bindingi165 – 172NADP8
Nucleotide bindingi509 – 513dUMP5
Nucleotide bindingi551 – 553dUMP3

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 4889
2.1.1.45 4889
SABIO-RKiP13922
UniPathwayi
UPA00077;UER00158

Protein family/group databases

MoonProtiP13922

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 falciparum (isolate K1 / Thailand)
Taxonomic identifieri5839 [NCBI]
Taxonomic lineageiEukaryotaAlveolataApicomplexaAconoidasidaHaemosporidaPlasmodiidaePlasmodiumPlasmodium (Laverania)

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL1939
DrugBankiDB01131 Proguanil
DB00205 Pyrimethamine
DB01299 Sulfadoxine

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001863491 – 608Bifunctional dihydrofolate reductase-thymidylate synthaseAdd BLAST608

Proteomic databases

PRIDEiP13922

Interactioni

Subunit structurei

Homodimer.1 Publication

Structurei

Secondary structure

1608
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP13922
SMRiP13922
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP13922

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini10 – 228DHFRAdd BLAST219

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni14 – 15Substrate binding2
Regioni322 – 608Thymidylate 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

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
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.

P13922-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MMEQVCDVFD IYAICACCKV ESKNEGKKNE VFNNYTFRGL GNKGVLPWKC
60 70 80 90 100
NSLDMKYFRA VTTYVNESKY EKLKYKRCKY LNKETVDNVN DMPNSKKLQN
110 120 130 140 150
VVVMGRTNWE SIPKKFKPLS NRINVILSRT LKKEDFDEDV YIINKVEDLI
160 170 180 190 200
VLLGKLNYYK CFIIGGSVVY QEFLEKKLIK KIYFTRINST YECDVFFPEI
210 220 230 240 250
NENEYQIISV SDVYTSNNTT LDFIIYKKTN NKMLNEQNCI KGEEKNNDMP
260 270 280 290 300
LKNDDKDTCH MKKLTEFYKN VDKYKINYEN DDDDEEEDDF VYFNFNKEKE
310 320 330 340 350
EKNKNSIHPN DFQIYNSLKY KYHPEYQYLN IIYDIMMNGN KQSDRTGVGV
360 370 380 390 400
LSKFGYIMKF DLSQYFPLLT TKKLFLRGII EELLWFIRGE TNGNTLLNKN
410 420 430 440 450
VRIWEANGTR EFLDNRKLFH REVNDLGPIY GFQWRHFGAE YTNMYDNYEN
460 470 480 490 500
KGVDQLKNII NLIKNDPTSR RILLCAWNVK DLDQMALPPC HILCQFYVFD
510 520 530 540 550
GKLSCIMYQR SCDLGLGVPF NIASYSIFTH MIAQVCNLQP AQFIHVLGNA
560 570 580 590 600
HVYNNHIDSL KIQLNRIPYP FPTLKLNPDI KNIEDFTISD FTIQNYVHHE

KISMDMAA
Length:608
Mass (Da):71,817
Last modified:August 1, 1990 - v2
Checksum:i7727EEB4A3946996
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti16A → V in strain: Isolate Palo-Alto. 1
Natural varianti51N → I. 1
Natural varianti59R → C in strain: Isolate FCR-3, Isolate Gambia and Isolate Palo-Alto. 1
Natural varianti108N → T in strain: Isolate FCR-3, Isolate Gambia and Isolate Palo-Alto. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M22159 Genomic DNA Translation: AAA29580.1
J04643 Genomic DNA Translation: AAA29586.1
J03772 Genomic DNA Translation: AAB59212.1
J03028 Genomic DNA Translation: AAA29585.1
PIRiA39975 RDZQK1

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M22159 Genomic DNA Translation: AAA29580.1
J04643 Genomic DNA Translation: AAA29586.1
J03772 Genomic DNA Translation: AAB59212.1
J03028 Genomic DNA Translation: AAA29585.1
PIRiA39975 RDZQK1

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1J3IX-ray2.33A/B1-280[»]
C/D281-608[»]
1J3JX-ray2.30A/B1-280[»]
C/D281-608[»]
1J3KX-ray2.10A/B1-280[»]
C/D281-608[»]
3DG8X-ray2.58A/B1-280[»]
C/D281-608[»]
3DGAX-ray2.70A/B1-280[»]
C/D281-608[»]
ProteinModelPortaliP13922
SMRiP13922
ModBaseiSearch...
MobiDBiSearch...

Chemistry databases

ChEMBLiCHEMBL1939
DrugBankiDB01131 Proguanil
DB00205 Pyrimethamine
DB01299 Sulfadoxine

Protein family/group databases

MoonProtiP13922

Proteomic databases

PRIDEiP13922

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Enzyme and pathway databases

UniPathwayi
UPA00077;UER00158

BRENDAi1.5.1.3 4889
2.1.1.45 4889
SABIO-RKiP13922

Miscellaneous databases

EvolutionaryTraceiP13922

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
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
ProtoNetiSearch...

Entry informationi

Entry nameiDRTS_PLAFK
AccessioniPrimary (citable) accession number: P13922
Secondary accession number(s): Q27734
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: August 1, 1990
Last modified: February 28, 2018
This is version 120 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)

Miscellaneousi

Keywords - Technical termi

3D-structure

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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