Reviewed, UniProtKB/Swiss-Prot P16126 (DRTS_LEIAM)

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 amazonensis
Taxonomic identifier	5659 [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	Inferred from homology.

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	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_0000186344
Regions
	Domain	26 – 229	204	DHFR
	Region	234 – 520	287	Thymidylate synthase
Sites
	Active site	400	1	By similarity

Sequences

	Sequence		Length	Mass (Da)
	P16126-1 [UniParc]. Last modified April 1, 1990. Version 1. Checksum: B59CEE0CC3CF7BED	FASTA	520	58,610
	10 20 30 40 50 60 MSRAAAKFKI PMPVTKADFA FPSLRAFSIV VALDKQHGIG DGESIPWRVP EDMAFFKDQT 70 80 90 100 110 120 TLLRNKKPPT DKKRNAVVMG RKTWESVPVK FRPLKGRLNV VLSSKATVEE LLAPLPEEKR 130 140 150 160 170 180 AAAAQDIVVV NGGLAAAVRL LARPPYCSSI ETAYCVGGAQ VYADAMLSPC VEKLQEVYLT 190 200 210 220 230 240 RIHTTAPACT RFFPFPPENA ATAWDLASSQ GRRKSAVDGL EFEICKYVPR NHEERQYLEL 250 260 270 280 290 300 IDRIMKTGIA KEDRTGVGTL SLFGAQMRFS LRDNRLPLLT TKRVFWRGVC EELLWFLRGE 310 320 330 340 350 360 TNAQLLADKD IHIWDGNGSR EFLDSRGLTE NTEMDLGPVY GFQWRHFGAE YRGLEANYDG 370 380 390 400 410 420 EGVDQIKFIV ETIKANPNDR RLLFTAWNPC ALHKMALPPC HLLAQFYVNT EKSELSCMLY 430 440 450 460 470 480 QRSCDMGLGV PFNIASYALL TILIAKATGL RPGELVHTLG DAHVYRSHID ALKAQLERVP 490 500 510 520 HAFPTLVFKE ERQFLEDYEL MDMEVIDYVP HPPIKMEMAV

References

[1]	"Sequence of the dihydrofolate reductase-thymidylate synthase (DHFR-TS) gene of Leishmania amazonensis." Nelson K., Alonso G., Langer P.J., Beverley S.M. Nucleic Acids Res. 18:2819-2819(1990) [PubMed: 2339068] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: MHOM/BR/77/LTB0016/C1S1.

Cross-references

Sequence databases
EMBLGenBankDDBJ	X51735 Genomic DNA. Translation: CAA36020.1.
PIR	RDLNTZ. S15756.
3D structure databases
HSSP	HSSP built from PDB template 1HVY based on UniProtKB P04818.
ModBase	Search...
Enzyme and pathway databases
BRENDA	1.5.1.3. 267701. 2.1.1.45. 267701.
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_LEIAM

Accession

Primary (citable) accession number: P16126

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	April 1, 1990
Last modified:	June 16, 2009
This is version 59 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)