Reviewed, UniProtKB/Swiss-Prot Q07422 (DRTS_TOXGO)

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	Toxoplasma gondii
Taxonomic identifier	5811 [NCBI]
Taxonomic lineage	Eukaryota › Alveolata › Apicomplexa › Coccidia › Eucoccidiorida › Eimeriorina › Sarcocystidae › Toxoplasma

Protein attributes

Sequence length	610 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	5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH. 5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP.
Pathway	Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate: step 1/1.
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 – 610	610	Bifunctional dihydrofolate reductase-thymidylate synthase		PRO_0000186352
Regions
	Domain	4 – 250	247	DHFR
	Nucleotide binding	16 – 22	7	NADP By similarity
	Nucleotide binding	81 – 83	3	NADP By similarity
	Nucleotide binding	102 – 105	4	NADP By similarity
	Nucleotide binding	152 – 159	8	NADP By similarity
	Nucleotide binding	509 – 513	5	dUMP By similarity
	Nucleotide binding	551 – 553	3	dUMP By similarity
	Region	322 – 610	289	Thymidylate synthase
Sites
	Active site	489	1	By similarity
	Binding site	8	1	Substrate; via carbonyl oxygen By similarity
	Binding site	10	1	NADP; via amide nitrogen and carbonyl oxygen By similarity
	Binding site	31	1	Substrate By similarity
	Binding site	157	1	Substrate By similarity
	Binding site	172	1	Substrate By similarity
	Binding site	344	1	dUMP By similarity
	Binding site	490	1	dUMP By similarity
	Binding site	521	1	dUMP By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q07422-1 [UniParc]. Last modified February 1, 1995. Version 1. Checksum: CFAF564416D04A29	FASTA	610	68,752
	10 20 30 40 50 60 MQKPVCLVVA MTPKRGIGIN NGLPWPHLTT DFKHFSRVTK TTPEEASRLN GWLPRKFAKT 70 80 90 100 110 120 GDSGLPSPSV GKRFNAVVMG RKTWESMPRK FRPLVDRLNI VVSSSLKEED IAAEKPQAEG 130 140 150 160 170 180 QQRVRVCASL PAALSLLEEE YKDSVDQIFV VGGAGLYEAA LSLGVASHLY ITRVAREFPC 190 200 210 220 230 240 DVFFPAFPGD DILSNKSTAA QAAAPAESVF VPFCPELGRE KDNEATYRPI FISKTFSDNG 250 260 270 280 290 300 VPYDFVVLEK RRKTDDAATA EPSNAMSSLT STRETTPVHG LQAPSSAAAI APVLAWMDEE 310 320 330 340 350 360 DRKKREQKEL IRAVPHVHFR GHEEFQYLDL IADIINNGRT MDDRTGVGVI SKFGCTMRYS 370 380 390 400 410 420 LDQAFPLLTT KRVFWKGVLE ELLWFIRGDT NANHLSEKGV KIWDKNVTRE FLDSRNLPHR 430 440 450 460 470 480 EVGDIGPGYG FQWRHFGAAY KDMHTDYTGQ GVDQLKNVIQ MLRTNPTDRR MLMTAWNPAA 490 500 510 520 530 540 LDEMALPPCH LLCQFYVNDQ KELSCIMYQR SCDVGLGVPF NIASYSLLTL MVAHVCNLKP 550 560 570 580 590 600 KEFIHFMGNT HVYTNHVEAL KEQLRREPRP FPIVNILNKE RIKEIDDFTA EDFEVVGYVP 610 HGRIQMEMAV

References

[1]	"Primary structure of the dihydrofolate reductase-thymidylate synthase gene from Toxoplasma gondii." Roos D.S. J. Biol. Chem. 268:6269-6280(1993) [PubMed: 8454599] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: RH.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L08489 Genomic DNA. Translation: AAB00163.1.
PIR	A46005.
3D structure databases
SMR	Q07422. Positions 322-610.
ModBase	Search...
Enzyme and pathway databases
BRENDA	1.5.1.3. 262552. 2.1.1.45. 262552.
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...
Other Resources
BindingDB	Q07422.

Entry information

Entry name

DRTS_TOXGO

Accession

Primary (citable) accession number: Q07422

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	February 1, 1995
Last modified:	February 9, 2010
This is version 54 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)