Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein
Submitted name:

Dihydrofolate reductase-thymidylate synthase

Gene

DHFR-TS

Organism
Plasmodium falciparum
Status
Unreviewed-Annotation score: Annotation score: 3 out of 5-Experimental evidence at protein leveli

Functioni

Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism.UniRule annotation

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei16 – 161NADP; via amide nitrogen and carbonyl oxygenCombined sources
Binding sitei40 – 401NADP; via carbonyl oxygenCombined sources
Binding sitei144 – 1441NADP; via carbonyl oxygenCombined sources
Active sitei490 – 4901UniRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi44 – 452NADPCombined sources
Nucleotide bindingi106 – 1083NADPCombined sources
Nucleotide bindingi127 – 1304NADPCombined sources
Nucleotide bindingi166 – 1727NADPCombined sources

GO - Molecular functioni

  1. dihydrofolate reductase activity Source: InterPro
  2. nucleotide binding Source: UniProtKB-KW
  3. thymidylate synthase activity Source: InterPro

GO - Biological processi

  1. dTMP biosynthetic process Source: InterPro
  2. glycine biosynthetic process Source: InterPro
  3. one-carbon metabolic process Source: UniProtKB-KW
  4. tetrahydrofolate biosynthetic process Source: UniProtKB-UniPathway
Complete GO annotation...

Keywords - Molecular functioni

MethyltransferaseUniRule annotation, OxidoreductaseUniRule annotation, Transferase

Keywords - Biological processi

Nucleotide biosynthesisUniRule annotation, One-carbon metabolismUniRule annotation

Keywords - Ligandi

NADPCombined sources, Nucleotide-bindingCombined sources

Enzyme and pathway databases

UniPathwayiUPA00077; UER00158.

Names & Taxonomyi

Protein namesi
Submitted name:
Dihydrofolate reductase-thymidylate synthaseImported
Submitted name:
Dihydrofolate reductase/thymidylate synthaseImported
Gene namesi
Name:DHFR-TSImported
Synonyms:dhfr-tsImported
OrganismiPlasmodium falciparumImported
Taxonomic identifieri5833 [NCBI]
Taxonomic lineageiEukaryotaAlveolataApicomplexaAconoidasidaHaemosporidaPlasmodiumPlasmodium (Laverania)

PTM / Processingi

Proteomic databases

PRIDEiA7UD81.

Interactioni

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3QGTX-ray2.30A/B1-608[»]
3UM5X-ray2.40A/B1-608[»]
3UM6X-ray2.65A/B1-608[»]
3UM8X-ray2.60A/B1-608[»]
4DPDX-ray2.50A/B1-608[»]
ProteinModelPortaliA7UD81.
SMRiA7UD81. Positions 1-608.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiA7UD81.

Family & Domainsi

Sequence similaritiesi

In the C-terminal section; belongs to the thymidylate synthase family.UniRule annotation
In the N-terminal section; belongs to the dihydrofolate reductase family.UniRule annotation

Family and domain databases

Gene3Di3.30.572.10. 1 hit.
3.40.430.10. 1 hit.
HAMAPiMF_00008. Thymidy_synth_bact.
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.

A7UD81-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MMEQVCDVFD IYAICACCKV ESKNEGKKNE VFNNYTFRGL GNKGVLPWKC
60 70 80 90 100
NSLDMKYFCA VTTYVNESKY EKLKYKRCKY LNKETVDNVN DMPNSKKLQN
110 120 130 140 150
VVVMGRTSWE 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):71,737
Last modified:October 1, 2007 - v1
Checksum:i26FD4BB4A5F1F4A7
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
EU046230 Genomic DNA. Translation: ABU43153.1.
EU046231 Genomic DNA. Translation: ABU43154.1.
EU046232 Genomic DNA. Translation: ABU43155.1.
EU046233 Genomic DNA. Translation: ABU43156.1.
EU682760 Genomic DNA. Translation: ACG59401.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
EU046230 Genomic DNA. Translation: ABU43153.1.
EU046231 Genomic DNA. Translation: ABU43154.1.
EU046232 Genomic DNA. Translation: ABU43155.1.
EU046233 Genomic DNA. Translation: ABU43156.1.
EU682760 Genomic DNA. Translation: ACG59401.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3QGTX-ray2.30A/B1-608[»]
3UM5X-ray2.40A/B1-608[»]
3UM6X-ray2.65A/B1-608[»]
3UM8X-ray2.60A/B1-608[»]
4DPDX-ray2.50A/B1-608[»]
ProteinModelPortaliA7UD81.
SMRiA7UD81. Positions 1-608.
ModBaseiSearch...
MobiDBiSearch...

Chemistry

BindingDBiA7UD81.

Proteomic databases

PRIDEiA7UD81.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Enzyme and pathway databases

UniPathwayiUPA00077; UER00158.

Miscellaneous databases

EvolutionaryTraceiA7UD81.

Family and domain databases

Gene3Di3.30.572.10. 1 hit.
3.40.430.10. 1 hit.
HAMAPiMF_00008. Thymidy_synth_bact.
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...

Publicationsi

  1. Cited for: NUCLEOTIDE SEQUENCE.
    Strain: 14290Imported, 18308Imported, 44200Imported and 45700Imported.
  2. "Analysis of drug resistance genes of Plasmodium falciparum in isolates from Bikaner, India."
    Garg S., Saxena V., Kochar D., Das A.
    Submitted (MAR-2008) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE.
    Strain: INBK1004Imported.
  3. "Trypanosomal dihydrofolate reductase reveals natural antifolate resistance."
    Vanichtanankul J., Taweechai S., Yuvaniyama J., Vilaivan T., Chitnumsub P., Kamchonwongpaisan S., Yuthavong Y.
    ACS Chem. Biol. 6:905-911(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH NADP.
  4. "Combined spatial limitation around residues 16 and 108 of Plasmodium falciparum dihydrofolate reductase explains resistance to cycloguanil."
    Vanichtanankul J., Taweechai S., Uttamapinant C., Chitnumsub P., Vilaivan T., Yuthavong Y., Kamchonwongpaisan S.
    Antimicrob. Agents Chemother. 56:3928-3935(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) IN COMPLEX WITH NADP.
  5. Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) IN COMPLEX WITH NADP.

Entry informationi

Entry nameiA7UD81_PLAFA
AccessioniPrimary (citable) accession number: A7UD81
Entry historyi
Integrated into UniProtKB/TrEMBL: October 1, 2007
Last sequence update: October 1, 2007
Last modified: March 31, 2015
This is version 58 of the entry and version 1 of the sequence. [Complete history]
Entry statusiUnreviewed (UniProtKB/TrEMBL)

Miscellaneousi

Keywords - Technical termi

3D-structureCombined sources

External Data

Dasty 3

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 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.