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Protein

Bifunctional dihydrofolate reductase-thymidylate synthase

Gene
N/A
Organism
Trypanosoma cruzi
Status
Reviewed-Annotation score: Annotation score: 5 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.

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, Bifunctional dihydrofolate reductase-thymidylate synthase, 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 sitei26Substrate; via carbonyl oxygen1
Binding sitei28NADP; via amide nitrogen and carbonyl oxygen1
Binding sitei48Substrate1
Binding sitei154Substrate; via carbonyl oxygen1
Binding sitei160Substrate1
Binding sitei178Substrate1
Binding sitei257dUMP1
Active sitei403By similarity1
Binding sitei404dUMP1
Binding sitei434dUMP1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi34 – 40NADP7
Nucleotide bindingi78 – 80NADP3
Nucleotide bindingi99 – 102NADP4
Nucleotide bindingi155 – 162NADP8
Nucleotide bindingi422 – 426dUMP5
Nucleotide bindingi464 – 466dUMP3

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. 6524.
2.1.1.45. 6524.
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)
OrganismiTrypanosoma cruzi
Taxonomic identifieri5693 [NCBI]
Taxonomic lineageiEukaryotaEuglenozoaKinetoplastidaTrypanosomatidaeTrypanosomaSchizotrypanum

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL1163130.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001863541 – 521Bifunctional dihydrofolate reductase-thymidylate synthaseAdd BLAST521

Proteomic databases

PaxDbiQ27793.

Interactioni

Subunit structurei

Homodimer.1 Publication

Protein-protein interaction databases

STRINGi353153.XP_815327.1.

Chemistry databases

BindingDBiQ27793.

Structurei

Secondary structure

1521
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi2 – 4Combined sources3
Turni10 – 13Combined sources4
Helixi14 – 16Combined sources3
Beta strandi23 – 30Combined sources8
Beta strandi33 – 39Combined sources7
Helixi46 – 57Combined sources12
Beta strandi60 – 63Combined sources4
Beta strandi70 – 77Combined sources8
Helixi78 – 82Combined sources5
Helixi86 – 88Combined sources3
Beta strandi94 – 99Combined sources6
Helixi105 – 110Combined sources6
Beta strandi112 – 114Combined sources3
Helixi115 – 121Combined sources7
Helixi122 – 124Combined sources3
Beta strandi125 – 130Combined sources6
Helixi132 – 139Combined sources8
Turni142 – 147Combined sources6
Beta strandi148 – 153Combined sources6
Helixi157 – 163Combined sources7
Helixi168 – 171Combined sources4
Beta strandi172 – 180Combined sources9
Beta strandi188 – 190Combined sources3
Helixi199 – 201Combined sources3
Beta strandi206 – 211Combined sources6
Beta strandi218 – 221Combined sources4
Beta strandi224 – 232Combined sources9
Helixi235 – 250Combined sources16
Beta strandi252 – 255Combined sources4
Beta strandi261 – 273Combined sources13
Helixi275 – 277Combined sources3
Beta strandi283 – 285Combined sources3
Helixi289 – 300Combined sources12
Helixi307 – 310Combined sources4
Turni311 – 313Combined sources3
Turni319 – 321Combined sources3
Helixi323 – 328Combined sources6
Helixi343 – 349Combined sources7
Beta strandi357 – 359Combined sources3
Helixi368 – 378Combined sources11
Beta strandi386 – 388Combined sources3
Turni392 – 394Combined sources3
Helixi395 – 397Combined sources3
Beta strandi398 – 400Combined sources3
Beta strandi403 – 412Combined sources10
Beta strandi415 – 426Combined sources12
Turni427 – 429Combined sources3
Helixi430 – 448Combined sources19
Beta strandi452 – 466Combined sources15
Helixi467 – 469Combined sources3
Helixi470 – 476Combined sources7
Beta strandi486 – 490Combined sources5
Helixi496 – 498Combined sources3
Helixi501 – 503Combined sources3
Beta strandi504 – 508Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2H2QX-ray2.40A/B1-521[»]
3CL9X-ray3.30A1-521[»]
3CLBX-ray3.00A/B/C/D1-521[»]
3HBBX-ray3.00A/B/C/D1-521[»]
3INVX-ray2.37A/B1-521[»]
3IRMX-ray2.10A/B/C/D1-521[»]
3IRNX-ray2.60A/B/C/D1-521[»]
3IROX-ray2.80A/B/C/D1-521[»]
ProteinModelPortaliQ27793.
SMRiQ27793.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ27793.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini22 – 232DHFRAdd BLAST211

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni237 – 521Thymidylate synthaseAdd BLAST285

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

eggNOGiENOG410K3YI. Eukaryota.
KOG0673. Eukaryota.
KOG1324. Eukaryota.
COG0207. LUCA.
COG0262. LUCA.

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.
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.

Q27793-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSLFKIRMPE TVAEGTRLAL RAFSLVVAVD EHGGIGDGRS IPWNVPEDMK
60 70 80 90 100
FFRDLTTKLR GKNVKPSPAK RNAVVMGRKT WDSIPPKFRP LPGRLNVVLS
110 120 130 140 150
STLTTQHLLD GLPDEEKRNL HADSIVAVNG GLEQALRLLA SPNYTPSIET
160 170 180 190 200
VYCIGGGSVY AEALRPPCVH LLQAIYRTTI RASESSCSVF FRVPESGTEA
210 220 230 240 250
AAGIEWQRET ISEELTSANG NETKYYFEKL IPRNREEEQY LSLVDRIIRE
260 270 280 290 300
GNVKHDRTGV GTLSIFGAQM RFSLRNNRLP LLTTKRVFWR GVCEELLWFL
310 320 330 340 350
RGETYAKKLS DKGVHIWDDN GSRAFLDSRG LTEYEEMDLG PVYGFQWRHF
360 370 380 390 400
GAAYTHHDAN YDGQGVDQIK AIVETLKTNP DDRRMLFTAW NPSALPRMAL
410 420 430 440 450
PPCHLLAQFY VSNGELSCML YQRSCDMGLG VPFNIASYAL LTILIAKATG
460 470 480 490 500
LRPGELVHTL GDAHVYSNHV EPCNEQLKRV PRAFPYLVFR REREFLEDYE
510 520
EGDMEVIDYA PYPPISMKMA V
Length:521
Mass (Da):58,853
Last modified:May 1, 1997 - v2
Checksum:iDCB9F8782855810C
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L22484 Genomic DNA. Translation: AAB49898.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L22484 Genomic DNA. Translation: AAB49898.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2H2QX-ray2.40A/B1-521[»]
3CL9X-ray3.30A1-521[»]
3CLBX-ray3.00A/B/C/D1-521[»]
3HBBX-ray3.00A/B/C/D1-521[»]
3INVX-ray2.37A/B1-521[»]
3IRMX-ray2.10A/B/C/D1-521[»]
3IRNX-ray2.60A/B/C/D1-521[»]
3IROX-ray2.80A/B/C/D1-521[»]
ProteinModelPortaliQ27793.
SMRiQ27793.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi353153.XP_815327.1.

Chemistry databases

BindingDBiQ27793.
ChEMBLiCHEMBL1163130.

Proteomic databases

PaxDbiQ27793.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

eggNOGiENOG410K3YI. Eukaryota.
KOG0673. Eukaryota.
KOG1324. Eukaryota.
COG0207. LUCA.
COG0262. LUCA.

Enzyme and pathway databases

UniPathwayiUPA00077; UER00158.
BRENDAi1.5.1.3. 6524.
2.1.1.45. 6524.

Miscellaneous databases

EvolutionaryTraceiQ27793.

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.
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...

Entry informationi

Entry nameiDRTS_TRYCR
AccessioniPrimary (citable) accession number: Q27793
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 1, 1997
Last modified: November 30, 2016
This is version 87 of the entry and version 2 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.