Reviewed, UniProtKB/Swiss-Prot Q27793 (DRTS_TRYCR)

Names and origin

Protein names	Recommended name:     Bifunctional dihydrofolate reductase-thymidylate synthase       Short name=DHFR-TS Including the following 2 domains:     1- Recommended name:             Dihydrofolate reductase               EC=1.5.1.3     2- Recommended name:             Thymidylate synthase               EC=2.1.1.45
Organism	Trypanosoma cruzi
Taxonomic identifier	5693 [NCBI]
Taxonomic lineage	Eukaryota › Euglenozoa › Kinetoplastida › Trypanosomatidae › Trypanosoma › Schizotrypanum

Protein attributes

Sequence length	521 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Catalytic activity	5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + NADPH. 5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP.
Pathway	Cofactor biosynthesis; tetrahydrofolate biosynthesis; tetrahydrofolate from dihydrofolate: step 1/1.
Miscellaneous	The reaction catalyzed by this enzyme represents an essential step for de novo glycine and purine synthesis, DNA precursor synthesis, and for the conversion of dUMP to dTMP.
Sequence similarities	In the N-terminal section; belongs to the dihydrofolate reductase family. In the C-terminal section; belongs to the thymidylate synthase family. Contains 1 DHFR (dihydrofolate reductase) domain.

Ontologies

Keywords
Biological process	Nucleotide biosynthesis One-carbon metabolism
Ligand	NADP
Molecular function	Methyltransferase Oxidoreductase Transferase
Technical term	3D-structure Multifunctional enzyme
Gene Ontology (GO)
Biological process	dTMP biosynthetic process Inferred from electronic annotation. Source: InterPro glycine biosynthetic process Inferred from electronic annotation. Source: InterPro one-carbon compound metabolic process Inferred from electronic annotation. Source: InterPro oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	dihydrofolate reductase activity Inferred from electronic annotation. Source: InterPro thymidylate synthase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 521	521	Bifunctional dihydrofolate reductase-thymidylate synthase		PRO_0000186354
Regions
	Domain	22 – 232	211	DHFR
	Region	237 – 521	285	Thymidylate synthase
Sites
	Active site	403	1	By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q27793-1 [UniParc]. Last modified May 1, 1997. Version 2. Checksum: DCB9F8782855810C	FASTA	521	58,853
	10 20 30 40 50 60 MSLFKIRMPE TVAEGTRLAL RAFSLVVAVD EHGGIGDGRS IPWNVPEDMK FFRDLTTKLR 70 80 90 100 110 120 GKNVKPSPAK RNAVVMGRKT WDSIPPKFRP LPGRLNVVLS STLTTQHLLD GLPDEEKRNL 130 140 150 160 170 180 HADSIVAVNG GLEQALRLLA SPNYTPSIET VYCIGGGSVY AEALRPPCVH LLQAIYRTTI 190 200 210 220 230 240 RASESSCSVF FRVPESGTEA AAGIEWQRET ISEELTSANG NETKYYFEKL IPRNREEEQY 250 260 270 280 290 300 LSLVDRIIRE GNVKHDRTGV GTLSIFGAQM RFSLRNNRLP LLTTKRVFWR GVCEELLWFL 310 320 330 340 350 360 RGETYAKKLS DKGVHIWDDN GSRAFLDSRG LTEYEEMDLG PVYGFQWRHF GAAYTHHDAN 370 380 390 400 410 420 YDGQGVDQIK AIVETLKTNP DDRRMLFTAW NPSALPRMAL PPCHLLAQFY VSNGELSCML 430 440 450 460 470 480 YQRSCDMGLG VPFNIASYAL LTILIAKATG LRPGELVHTL GDAHVYSNHV EPCNEQLKRV 490 500 510 520 PRAFPYLVFR REREFLEDYE EGDMEVIDYA PYPPISMKMA V

References

[1]	"Cloning and expression of the dihydrofolate reductase-thymidylate synthase gene from Trypanosoma cruzi." Reche P., Arrebola R., Olmo A., Santi D.V., Gonzalez-Pacanowska D., Ruiz-Perez L.M. Mol. Biochem. Parasitol. 65:247-258(1994) [PubMed: 7969266] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Y.
[2]	"Expression and characterization of the Trypanosoma cruzi dihydrofolate reductase domain." Reche P., Arrebola R., Santi D.V., Gonzalez-Pacanowska D., Ruiz-Perez L.M. Mol. Biochem. Parasitol. 76:175-185(1996) [PubMed: 8920005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Y.

Cross-references

Sequence databases

EMBLGenBankDDBJ

L22484 Genomic DNA. Translation: AAB49898.1.

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2H2Q	X-ray	2.40	A/B	1-521	[»]

ModBase

Search...

Family and domain databases

InterPro

IPR012262. DHFR-TS.
IPR001796. DHFR_reg.
IPR000398. Thymidylat_synth_C.
[Graphical view]

Gene3D

G3DSA:3.30.572.10. Thymidylat_synth_C. 1 hit.

PANTHER

PTHR11549:SF2. Thymidylat_synth_C. 1 hit.

Pfam

PF00186. DHFR_1. 1 hit.
PF00303. Thymidylat_synt. 1 hit.
[Graphical view]

PIRSF

PIRSF000389. DHFR-TS. 1 hit.

PRINTS

PR00070. DHFR.
PR00108. THYMDSNTHASE.

ProDom

PD001180. Thymidylat_synth. 1 hit.
[Graphical view] [Entries sharing at least one domain]

TIGRFAMs

TIGR03284. thym_sym. 1 hit.

PROSITE

PS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
PS00091. THYMIDYLATE_SYNTHASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

DRTS_TRYCR

Accession

Primary (citable) accession number: Q27793

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	May 1, 1997
Last modified:	November 25, 2008
This is version 43 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)