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Q27713

- DRTS_PLABA

UniProt

Q27713 - DRTS_PLABA

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Protein

Bifunctional dihydrofolate reductase-thymidylate synthase

Gene
N/A
Organism
Plasmodium berghei (strain Anka)
Status
Reviewed - 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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei51 – 511SubstrateBy similarity
Binding sitei173 – 1731Substrate; via carbonyl oxygenBy similarity
Binding sitei179 – 1791SubstrateBy similarity
Binding sitei194 – 1941SubstrateBy similarity
Binding sitei324 – 3241dUMPBy similarity
Active sitei469 – 4691By similarity
Binding sitei470 – 4701dUMPBy similarity
Binding sitei500 – 5001dUMPBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi36 – 427NADPBy similarity
Nucleotide bindingi108 – 1103NADPBy similarity
Nucleotide bindingi129 – 1324NADPBy similarity
Nucleotide bindingi174 – 1818NADPBy similarity
Nucleotide bindingi488 – 4925dUMPBy similarity
Nucleotide bindingi530 – 5323dUMPBy similarity

GO - Molecular functioni

  1. dihydrofolate reductase activity Source: UniProtKB-EC
  2. thymidylate synthase activity Source: UniProtKB-EC

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

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 lineageiEukaryotaAlveolataApicomplexaAconoidasidaHaemosporidaPlasmodiumPlasmodium (Vinckeia)

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 587587Bifunctional dihydrofolate reductase-thymidylate synthasePRO_0000186347Add
BLAST

Interactioni

Subunit structurei

Homodimer.By similarity

Structurei

3D structure databases

ProteinModelPortaliQ27713.
SMRiQ27713. Positions 1-238, 264-587.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini9 – 237229DHFRAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni301 – 587287Thymidylate synthaseAdd
BLAST

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

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.

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti110 – 1101S → N in pyrimethamine resistance.
Natural varianti177 – 1771S → F in pyrimethamine resistance.

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U12275 Genomic DNA. Translation: AAB60237.1.
L28119 Genomic DNA. Translation: AAA29581.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U12275 Genomic DNA. Translation: AAB60237.1 .
L28119 Genomic DNA. Translation: AAA29581.1 .

3D structure databases

ProteinModelPortali Q27713.
SMRi Q27713. Positions 1-238, 264-587.
ModBasei Search...
MobiDBi Search...

Chemistry

ChEMBLi CHEMBL3963.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Phylogenomic databases

HOGENOMi HOG000257901.

Enzyme and pathway databases

UniPathwayi UPA00077 ; UER00158 .

Family and domain databases

Gene3Di 3.30.572.10. 1 hit.
3.40.430.10. 1 hit.
HAMAPi MF_00008. Thymidy_synth_bact.
InterProi IPR024072. 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 ]
Pfami PF00186. DHFR_1. 1 hit.
PF00303. Thymidylat_synt. 1 hit.
[Graphical view ]
PIRSFi PIRSF000389. DHFR-TS. 1 hit.
PRINTSi PR00108. THYMDSNTHASE.
SUPFAMi SSF53597. SSF53597. 1 hit.
SSF55831. SSF55831. 1 hit.
TIGRFAMsi TIGR03284. thym_sym. 1 hit.
PROSITEi PS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
PS00091. THYMIDYLATE_SYNTHASE. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "Mechanisms of pyrimethamine resistance in two different strains of Plasmodium berghei."
    van Dijk M.R., McConkey G.A., Vinkenoog R., Waters A.P., Janse C.J.
    Mol. Biochem. Parasitol. 68:167-171(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "The dihydrofolate reductase domain of rodent malarias: point mutations and pyrimethamine resistance."
    Cheng Q., Saul A.
    Mol. Biochem. Parasitol. 65:361-363(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 12-201.

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: October 29, 2014
This is version 79 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

External Data

Dasty 3