Reviewed, UniProtKB/Swiss-Prot Q27783 (DRTS_TRYBB)

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 brucei brucei
Taxonomic identifier	5702 [NCBI]
Taxonomic lineage	Eukaryota › Euglenozoa › Kinetoplastida › Trypanosomatidae › Trypanosoma

Protein attributes

Sequence length	527 AA.
Sequence status	Complete.
Protein existence	Inferred from homology.

General annotation (Comments)

Function	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.
Catalytic activity	5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP. 5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH.
Pathway	Pyrimidine metabolism; dTTP biosynthesis. Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate: step 1/1.
Subunit structure	Homodimer By similarity.
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	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 metabolic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	dihydrofolate reductase activity Inferred from electronic annotation. Source: EC thymidylate synthase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 527	527	Bifunctional dihydrofolate reductase-thymidylate synthase		PRO_0000186353
Regions
	Domain	28 – 238	211	DHFR
	Nucleotide binding	40 – 46	7	NADP By similarity
	Nucleotide binding	84 – 86	3	NADP By similarity
	Nucleotide binding	105 – 108	4	NADP By similarity
	Nucleotide binding	161 – 168	8	NADP By similarity
	Nucleotide binding	428 – 432	5	dUMP By similarity
	Nucleotide binding	470 – 472	3	dUMP By similarity
	Region	243 – 527	285	Thymidylate synthase
Sites
	Active site	409	1	By similarity
	Binding site	32	1	Substrate; via carbonyl oxygen By similarity
	Binding site	34	1	NADP; via amide nitrogen and carbonyl oxygen By similarity
	Binding site	54	1	Substrate By similarity
	Binding site	160	1	Substrate; via carbonyl oxygen By similarity
	Binding site	166	1	Substrate By similarity
	Binding site	184	1	Substrate By similarity
	Binding site	263	1	dUMP By similarity
	Binding site	410	1	dUMP By similarity
	Binding site	440	1	dUMP By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q27783-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 39982FC553BF7601	FASTA	527	58,805
	10 20 30 40 50 60 MLSLTRILRK KIPVHELAGK ISRPPLRPFS VVVASDEKGG IGDGGTIPWE IPEDMQYFRR 70 80 90 100 110 120 VTTNLRGKNV KPSPSKRNAV VMGRKTWDSL PPKFRPLSNR LNVVLSRSAT KEQLLAGIPD 130 140 150 160 170 180 PIKRAEAAND VVAVNGGLED ALRMLVSKEH TSSIETVFCI GGGTIYKQAL CAPCVNVLQA 190 200 210 220 230 240 IHRTVVRPAS NSCSVFFDIP AAGTKTPEGL ELVRESITDE RVSTGAGGKK YQFEKLVPRN 250 260 270 280 290 300 SEEEQYLNLV GRIIDEGCTK CDRTGVGTRS LFGAQMRFSL RNNRLPLLTT KRVFWRGVCE 310 320 330 340 350 360 ELLWFLRGET NAKLLSDKGI HIWDGNGSRA FLDSRGLTDY DEMDLGPVYG FQWRHFGADY 370 380 390 400 410 420 ISCKVDSEGK GVDQIANIVK SLIENPDDRR MICTAWNPAA LPRMALPPCH MMAQFYVSNG 430 440 450 460 470 480 ELSCMLYQRS CDMGLGVPFN IASYALLTFL MAKASGLRPG ELVHTLGDAH VYSNHVEPCR 490 500 510 520 KQLKRVPRPF PFIVFKQDKE FLEDFQESDI EVIDYSPYPV ISMEMAV

References

[1]

"Trypanosoma brucei dihydrofolate reductase-thymidylate synthase: gene isolation and expression and characterization of the enzyme." Gamarro F., Yu P.L., Zhao J., Edman U., Greene P.J., Santi D. Mol. Biochem. Parasitol. 72:11-22(1995) [PubMed: 8538681] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: 427.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U20781 Genomic DNA. Translation: AAA91362.1.
3D structure databases
SMR	Q27783. Positions 11-521.
ModBase	Search...
Enzyme and pathway databases
BRENDA	1.5.1.3. 74165. 2.1.1.45. 74165.
Family and domain databases
InterPro	IPR012262. DHFR-TS. IPR017925. Dihydrofolate_reductase_CS. IPR001796. Dihydrofolate_reductase_dom. IPR000398. Thymidylate_synthase. IPR020940. Thymidylate_synthase_AS. [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	PR00108. THYMDSNTHASE.
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_TRYBB

Accession

Primary (citable) accession number: Q27783

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	February 9, 2010
This is version 58 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)