Reviewed, UniProtKB/Swiss-Prot Q23695 (DRTS_CRIFA)

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	Crithidia fasciculata
Taxonomic identifier	5656 [NCBI]
Taxonomic lineage	Eukaryota › Euglenozoa › Kinetoplastida › Trypanosomatidae › Crithidia

Protein attributes

Sequence length	515 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: 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 – 515	515	Bifunctional dihydrofolate reductase-thymidylate synthase		PRO_0000186343
Regions
	Domain	26 – 228	203	DHFR
	Region	233 – 515	283	Thymidylate synthase
Sites
	Active site	385	1	By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q23695-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 8327DAB231535921	FASTA	515	58,294
	10 20 30 40 50 60 MSRAAAKFKI PMPVTKADFA FPSLRAFSIV VAADQQHGIG DGETIPWTVP ETLAFFKDQT 70 80 90 100 110 120 TLLRNKKPPT EKKRNAVVMG RKTWEVPLKF RPLKGRLNVV LSCRRPVDDL LAQLPEEKRA 130 140 150 160 170 180 AAAADVVING GLKEALHLLA RPPYCSSIET AYCIGGARVY TEAMQSPCVE KLKEVYLTRV 190 200 210 220 230 240 HTAPTCNRFY EFVRRRRARA AVDLESTSGV KVSDAAAHLS YEIMKYVPHN AEERQYLELI 250 260 270 280 290 300 DRIMKTGLVK EDRTGVGTIS LFGAQMFSLR DNQLPLLTTK RVFWRGVCEE LIWFLRGETN 310 320 330 340 350 360 AHVLADKDIH IWDGNGSREF LDSRGLTENK EMDLGPVYGF QWRHFGADYK GFDANYDEGV 370 380 390 400 410 420 DQIKTIVETL KTNDRRLLVT AWNPCALHKM AVRPCHLLGQ FYVNTQTKEL SCMLYQRCCD 430 440 450 460 470 480 MGLGVPFNIA SYALLTILIA KATGLRPGEL VHTLGTAHVY SNHVEALKEQ LQRVPVAFPV 490 500 510 LVFKKEREFL EDYESTDMEV VDYVPYPPIK MEMAV

References

[1]

"Structure, genomic organization and transcription of the bifunctional dihydrofolate reductase-thymidylate synthase gene from Crithidia fasciculata." Hughes D.E., Shonekan O.A., Simpson L. Mol. Biochem. Parasitol. 34:155-166(1989) [PubMed: 2540436] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].

Cross-references

Sequence databases
EMBLGenBankDDBJ	M22852 Genomic DNA. Translation: AAA30318.1.
3D structure databases
HSSP	HSSP built from PDB template 1HW4 based on UniProtKB P04818.
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. False negative. PS51330. DHFR_2. 1 hit. PS00091. THYMIDYLATE_SYNTHASE. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

DRTS_CRIFA

Accession

Primary (citable) accession number: Q23695

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	November 25, 2008
This is version 43 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)