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Protein

Bifunctional dihydrofolate reductase-thymidylate synthase

Gene
N/A
Organism
Trypanosoma cruzi
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.

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 (C3747_54g197), Bifunctional dihydrofolate reductase-thymidylate synthase (C4B63_30g231)
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

Keywordsi

Molecular functionMethyltransferase, Multifunctional enzyme, Oxidoreductase, Transferase
Biological processNucleotide biosynthesis, One-carbon metabolism
LigandNADP

Enzyme and pathway databases

BRENDAi1.5.1.3 6524
2.1.1.45 6524
SABIO-RKiQ27793
UniPathwayi
UPA00077;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

PRIDEiQ27793

Interactioni

Subunit structurei

Homodimer.1 Publication

Chemistry databases

BindingDBiQ27793

Structurei

Secondary structure

1521
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
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
PANTHERiPTHR11548:SF7 PTHR11548:SF7, 2 hits
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.

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

Similar proteinsi

Entry informationi

Entry nameiDRTS_TRYCR
AccessioniPrimary (citable) accession number: Q27793
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 1, 1997
Last modified: May 23, 2018
This is version 95 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)

Miscellaneousi

Keywords - Technical termi

3D-structure
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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