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

Comments

CATALYTIC ACTIVITY: 5,6,7,8-tetrahydrofolate + NADP⁺ = 7,8-dihydrofolate + NADPH.
CATALYTIC ACTIVITY: 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.
SIMILARITY: In the N-terminal section; belongs to the dihydrofolate reductase family.
SIMILARITY: In the C-terminal section; belongs to the thymidylate synthase family.
SIMILARITY: Contains 1 DHFR (dihydrofolate reductase) domain.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

M12734; AAA29232.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
M14330; AAA29272.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
X51733; CAA36019.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

PIR

A23403; RDLNTS.

3D structure databases

HSSP

P04818; 1HW4. [HSSP ENTRY / PDB]

ModBase

P07382.

Ontologies

GO:0055114;	Biological process: oxidation reduction (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.

Family and domain databases

InterPro

IPR012262; DHFR-TS.
IPR001796; DHFR_reg.
IPR000398; Thymidylat_synth_C.
Graphical view of domain structure.

Gene3D

G3DSA:3.30.572.10; Thymidylat_synth_C; 1.

PANTHER

PTHR11549:SF2; Thymidylat_synth_C; 1.

Pfam

PF00186; DHFR_1; 1.
PF00303; Thymidylat_synt; 1.
Pfam graphical view of domain structure.

PIRSF

PIRSF000389; DHFR-TS; 1.

PRINTS

PR00070; DHFR.
PR00108; THYMDSNTHASE.

ProDom

PD001180; Thymidylat_synth; 1.
[Domain structure / List of seq. sharing at least 1 domain]

TIGRFAMs

TIGR03284; thym_sym; 1.

PROSITE

PS00075; DHFR_1; 1.
PS51330; DHFR_2; 1.
PS00091; THYMIDYLATE_SYNTHASE; 1.
PROSITE graphical view of domain structure (profiles).

Other

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Direct protein sequencing; Methyltransferase; Multifunctional enzyme; NADP; Nucleotide biosynthesis; One-carbon metabolism; Oxidoreductase; Transferase.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 520`	`520`	`Bifunctional dihydrofolate reductase-thymidylate synthase.`	`PRO_0000186345`
`DOMAIN`	`26 229`	`204`	`DHFR.`
`REGION`	`234 520`	`287`	`Thymidylate synthase.`
`ACT_SITE`	`400 400`		`By similarity.`
`CONFLICT`	`28 28`		`S -> C (in Ref. 2; AAA29272).`
`CONFLICT`	`49 49`		`V -> S (in Ref. 2; AAA29272).`
`CONFLICT`	`72 76`		`KKRNA -> EEAQR (in Ref. 2; AAA29272).`
`CONFLICT`	`125 127`		`QDV -> RML (in Ref. 2; AAA29272).`
`CONFLICT`	`307 307`		`A -> T (in Ref. 2; AAA29272).`
`CONFLICT`	`397 397`		`L -> V (in Ref. 2; AAA29272).`

Sequence information

Length: 520 AA [This is the length of the unprocessed precursor]

Molecular weight: 58689 Da [This is the MW of the unprocessed precursor]

CRC64: 7D221F2CF2BE43D4 [This is a checksum on the sequence]

        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

P07382 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools