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Protein

Bifunctional dihydrofolate reductase-thymidylate synthase

Gene
N/A
Organism
Toxoplasma gondii
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-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 (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 sitei8Substrate; via carbonyl oxygenBy similarity1
Binding sitei10NADP; via amide nitrogen and carbonyl oxygenBy similarity1
Binding sitei31SubstrateBy similarity1
Binding sitei157SubstrateBy similarity1
Binding sitei172SubstrateBy similarity1
Binding sitei344dUMPBy similarity1
Active sitei489By similarity1
Binding sitei490dUMPBy similarity1
Binding sitei521dUMPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi16 – 22NADPBy similarity7
Nucleotide bindingi81 – 83NADPBy similarity3
Nucleotide bindingi102 – 105NADPBy similarity4
Nucleotide bindingi152 – 159NADPBy similarity8
Nucleotide bindingi509 – 513dUMPBy similarity5
Nucleotide bindingi551 – 553dUMPBy 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

BRENDAi1.5.1.3. 6411.
SABIO-RKQ07422.
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)
OrganismiToxoplasma gondii
Taxonomic identifieri5811 [NCBI]
Taxonomic lineageiEukaryotaAlveolataApicomplexaConoidasidaCoccidiaEucoccidioridaEimeriorinaSarcocystidaeToxoplasma

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2425.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001863521 – 610Bifunctional dihydrofolate reductase-thymidylate synthaseAdd BLAST610

Interactioni

Protein-protein interaction databases

STRINGi5811.TGME49_049180.

Chemistry databases

BindingDBiQ07422.

Structurei

Secondary structure

1610
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi5 – 11Combined sources7
Beta strandi16 – 19Combined sources4
Beta strandi24 – 26Combined sources3
Helixi29 – 40Combined sources12
Beta strandi74 – 80Combined sources7
Helixi81 – 86Combined sources6
Helixi89 – 91Combined sources3
Beta strandi97 – 102Combined sources6
Helixi108 – 114Combined sources7
Beta strandi125 – 129Combined sources5
Helixi130 – 141Combined sources12
Turni142 – 144Combined sources3
Beta strandi145 – 150Combined sources6
Helixi154 – 163Combined sources10
Beta strandi166 – 174Combined sources9
Beta strandi181 – 183Combined sources3
Helixi190 – 192Combined sources3
Beta strandi227 – 232Combined sources6
Beta strandi236 – 238Combined sources3
Beta strandi241 – 250Combined sources10
Turni288 – 290Combined sources3
Helixi291 – 297Combined sources7
Beta strandi318 – 320Combined sources3
Helixi325 – 337Combined sources13
Beta strandi339 – 341Combined sources3
Beta strandi349 – 360Combined sources12
Beta strandi362 – 364Combined sources3
Beta strandi369 – 371Combined sources3
Helixi375 – 386Combined sources12
Helixi393 – 396Combined sources4
Turni397 – 399Combined sources3
Helixi404 – 406Combined sources3
Helixi409 – 414Combined sources6
Helixi429 – 435Combined sources7
Beta strandi450 – 452Combined sources3
Helixi454 – 464Combined sources11
Beta strandi472 – 474Combined sources3
Turni478 – 480Combined sources3
Helixi481 – 483Combined sources3
Beta strandi484 – 486Combined sources3
Beta strandi489 – 497Combined sources9
Beta strandi501 – 513Combined sources13
Turni514 – 516Combined sources3
Helixi517 – 535Combined sources19
Beta strandi539 – 553Combined sources15
Helixi554 – 556Combined sources3
Helixi557 – 563Combined sources7
Beta strandi573 – 577Combined sources5
Helixi579 – 581Combined sources3
Helixi585 – 587Combined sources3
Beta strandi592 – 597Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4ECKX-ray3.52A/B1-610[»]
4EILX-ray2.20A/B/C/D/E/F/G/H1-610[»]
4KY4X-ray2.79A/B/C/D/E/F/G/H1-610[»]
4KYAX-ray3.26A/B/C/D/E/F/G/H1-610[»]
5T0LX-ray3.13A/B1-610[»]
ProteinModelPortaliQ07422.
SMRiQ07422.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 250DHFRAdd BLAST247

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni322 – 610Thymidylate synthaseAdd BLAST289

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.
OMAiNPVKKDI.

Family and domain databases

CDDicd00209. DHFR. 1 hit.
cd00351. TS_Pyrimidine_HMase. 1 hit.
Gene3Di3.30.572.10. 1 hit.
3.40.430.10. 2 hits.
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. 2 hits.
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.

Q07422-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQKPVCLVVA MTPKRGIGIN NGLPWPHLTT DFKHFSRVTK TTPEEASRLN
60 70 80 90 100
GWLPRKFAKT GDSGLPSPSV GKRFNAVVMG RKTWESMPRK FRPLVDRLNI
110 120 130 140 150
VVSSSLKEED IAAEKPQAEG QQRVRVCASL PAALSLLEEE YKDSVDQIFV
160 170 180 190 200
VGGAGLYEAA LSLGVASHLY ITRVAREFPC DVFFPAFPGD DILSNKSTAA
210 220 230 240 250
QAAAPAESVF VPFCPELGRE KDNEATYRPI FISKTFSDNG VPYDFVVLEK
260 270 280 290 300
RRKTDDAATA EPSNAMSSLT STRETTPVHG LQAPSSAAAI APVLAWMDEE
310 320 330 340 350
DRKKREQKEL IRAVPHVHFR GHEEFQYLDL IADIINNGRT MDDRTGVGVI
360 370 380 390 400
SKFGCTMRYS LDQAFPLLTT KRVFWKGVLE ELLWFIRGDT NANHLSEKGV
410 420 430 440 450
KIWDKNVTRE FLDSRNLPHR EVGDIGPGYG FQWRHFGAAY KDMHTDYTGQ
460 470 480 490 500
GVDQLKNVIQ MLRTNPTDRR MLMTAWNPAA LDEMALPPCH LLCQFYVNDQ
510 520 530 540 550
KELSCIMYQR SCDVGLGVPF NIASYSLLTL MVAHVCNLKP KEFIHFMGNT
560 570 580 590 600
HVYTNHVEAL KEQLRREPRP FPIVNILNKE RIKEIDDFTA EDFEVVGYVP
610
HGRIQMEMAV
Length:610
Mass (Da):68,752
Last modified:February 1, 1995 - v1
Checksum:iCFAF564416D04A29
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L08489 Genomic DNA. Translation: AAB00163.1.
PIRiA46005.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L08489 Genomic DNA. Translation: AAB00163.1.
PIRiA46005.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4ECKX-ray3.52A/B1-610[»]
4EILX-ray2.20A/B/C/D/E/F/G/H1-610[»]
4KY4X-ray2.79A/B/C/D/E/F/G/H1-610[»]
4KYAX-ray3.26A/B/C/D/E/F/G/H1-610[»]
5T0LX-ray3.13A/B1-610[»]
ProteinModelPortaliQ07422.
SMRiQ07422.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi5811.TGME49_049180.

Chemistry databases

BindingDBiQ07422.
ChEMBLiCHEMBL2425.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

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

Enzyme and pathway databases

UniPathwayiUPA00077; UER00158.
BRENDAi1.5.1.3. 6411.
SABIO-RKQ07422.

Family and domain databases

CDDicd00209. DHFR. 1 hit.
cd00351. TS_Pyrimidine_HMase. 1 hit.
Gene3Di3.30.572.10. 1 hit.
3.40.430.10. 2 hits.
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. 2 hits.
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_TOXGO
AccessioniPrimary (citable) accession number: Q07422
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: November 30, 2016
This is version 94 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)

Miscellaneousi

Keywords - Technical termi

3D-structure, Multifunctional enzyme

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.