Reviewed, UniProtKB/Swiss-Prot P07382 (DRTS_LEIMA)

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	Leishmania major
Taxonomic identifier	5664 [NCBI]
Taxonomic lineage	Eukaryota › Euglenozoa › Kinetoplastida › Trypanosomatidae › Leishmania

Protein attributes

Sequence length	520 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	Direct protein sequencing 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: 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 – 520	520	Bifunctional dihydrofolate reductase-thymidylate synthase		PRO_0000186345
Regions
	Domain	26 – 229	204	DHFR
	Region	234 – 520	287	Thymidylate synthase
Sites
	Active site	400	1	By similarity
Experimental info
	Sequence conflict	28	1	S → C in AAA29272. Ref.2
	Sequence conflict	49	1	V → S in AAA29272. Ref.2
	Sequence conflict	72 – 76	5	KKRNA → EEAQR in AAA29272. Ref.2
	Sequence conflict	125 – 127	3	QDV → RML in AAA29272. Ref.2
	Sequence conflict	307	1	A → T in AAA29272. Ref.2
	Sequence conflict	397	1	L → V in AAA29272. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P07382-1 [UniParc]. Last modified April 1, 1988. Version 1. Checksum: 7D221F2CF2BE43D4	FASTA	520	58,689
	10 20 30 40 50 60 MSRAAARFKI PMPETKADFA FPSLRAFSIV VALDMQHGIG DGESIPWRVP EDMTFFKNQT 70 80 90 100 110 120 TLLRNKKPPT EKKRNAVVMG RKTWESVPVK FRPLKGRLNI VLSSKATVEE LLAPLPEGQR 130 140 150 160 170 180 AAAAQDVVVV NGGLAEALRL LARPLYCSSI ETAYCVGGAQ VYADAMLSPC IEKLQEVYLT 190 200 210 220 230 240 RIYATAPACT RFFPFPPENA ATAWDLASSQ GRRKSEAEGL EFEICKYVPR NHEERQYLEL 250 260 270 280 290 300 IDRIMKTGIV KEDRTGVGTI SLFGAQMRFS LRDNRLPLLT TKRVFWRGVC EELLWFLRGE 310 320 330 340 350 360 TSAQLLADKD IHIWDGNGSR EFLDSRGLTE NKEMDLGPVY GFQWRHFGAD YKGFEANYDG 370 380 390 400 410 420 EGVDQIKLIV ETIKTNPNDR RLLVTAWNPC ALQKMALPPC HLLAQFYVNT DTSELSCMLY 430 440 450 460 470 480 QRSCDMGLGV PFNIASYALL TILIAKATGL RPGELVHTLG DAHVYRNHVD ALKAQLERVP 490 500 510 520 HAFPTLIFKE ERQYLEDYEL TDMEVIDYVP HPAIKMEMAV

References

[1]	"Primary structure of the gene encoding the bifunctional dihydrofolate reductase-thymidylate synthase of Leishmania major." Beverley S.M., Ellenberger T.E., Cordingley J.S. Proc. Natl. Acad. Sci. U.S.A. 83:2584-2588(1986) [PubMed: 3458220] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Bifunctional thymidylate synthase-dihydrofolate reductase from Leishmania tropica: sequence homology with the corresponding monofunctional proteins." Grumont R., Washtien W.L., Caput D., Santi D.V. Proc. Natl. Acad. Sci. U.S.A. 83:5387-5391(1986) [PubMed: 3461439] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	Kapler G.M., Zhang K., Beverley S. Submitted (FEB-1990) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: LT25Z.
[4]	"Limited proteolysis of the bifunctional thymidylate synthase-dihydrofolate reductase from Leishmania tropica." Garvey E.P., Santi D.V. Proc. Natl. Acad. Sci. U.S.A. 82:7188-7192(1985) [PubMed: 3903747] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE OF 334-361.

Cross-references

Sequence databases
EMBLGenBankDDBJ	M12734 Genomic DNA. Translation: AAA29232.1. M14330 Genomic DNA. Translation: AAA29272.1. X51733 Genomic DNA. Translation: CAA36019.1.
PIR	RDLNTS. A23403.
3D structure databases
HSSP	HSSP built from PDB template 1HW4 based on UniProtKB P04818.
ModBase	Search...
Phylogenomic databases
OMA	P07382. HADYTGK.
Enzyme and pathway databases
BRENDA	1.5.1.3. 19061. 2.1.1.45. 19061.
Family and domain databases
InterPro	IPR012262. DHFR-TS. IPR001796. DHFR_reg. IPR017925. Dihydrofolate_reductase_CS. 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	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_LEIMA

Accession

Primary (citable) accession number: P07382

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	April 1, 1988
Last modified:	June 16, 2009
This is version 64 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)