[1]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. DOI=10.1016/0166-6851(94)00163-4; PubMed=7891743 [NCBI, ExPASy, EBI, Israel, Japan] van Dijk M.R., McConkey G.A., Vinkenoog R., Waters A.P., Janse C.J.; "Mechanisms of pyrimethamine resistance in two different strains of Plasmodium berghei."; Mol. Biochem. Parasitol. 68:167-171(1994).
[2]	NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 12-201. DOI=10.1016/0166-6851(94)90087-6; PubMed=7969277 [NCBI, ExPASy, EBI, Israel, Japan] Cheng Q., Saul A.; "The dihydrofolate reductase domain of rodent malarias: point mutations and pyrimethamine resistance."; Mol. Biochem. Parasitol. 65:361-363(1994).

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

U12275; AAB60237.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
L28119; AAA29581.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

3D structure databases

HSSP

P13922; 1J3K. [HSSP ENTRY / PDB]

SMR

Q27713; 264-587.

ModBase

Q27713.

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).

BLOCKS

Q27713.

Other

DrugBank

DB00440; Trimethoprim.

ProtoNet

Q27713.

UniRef

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

Keywords

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

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 587`	`587`	`Bifunctional dihydrofolate reductase-thymidylate synthase.`	`PRO_0000186347`
`DOMAIN`	`9 237`	`229`	`DHFR.`
`REGION`	`301 587`	`287`	`Thymidylate synthase.`
`ACT_SITE`	`469 469`		`By similarity.`
`VARIANT`	`110 110`	`1`	`S -> N (in pyrimethamine resistance).`
`VARIANT`	`177 177`	`1`	`S -> F (in pyrimethamine resistance).`

Sequence information

Length: 587 AA [This is the length of the unprocessed precursor]

Molecular weight: 68932 Da [This is the MW of the unprocessed precursor]

CRC64: 6E638C2B02FEC13A [This is a checksum on the sequence]

        10         20         30         40         50         60 
MEDLSETFDI YAICACCKVL NDDEKVRCFN NKTFKGIGNA GVLPWKCNLI DMKYFSSVTS 

        70         80         90        100        110        120 
YINENNYIRL KWKRDKYMEK HNLKNNVELN TNIISSTNNL QNIVVMGKKS WESIPKKFKP 

       130        140        150        160        170        180 
LQNRINIILS RTLKKEDIVN ENNNENNNVI IIKSVDDLFP ILKCTKYYKC FIIGGSSVYK 

       190        200        210        220        230        240 
EFLDRNLIKK IYFTRINNSY NCDVLFPEIN ENLFKITSIS DVYYSNNTTL DFIIYSKTKE 

       250        260        270        280        290        300 
INPNEEVPNN TFLGVCDEQN KAFDDEDDYT YFSFNKNKEN IKKNSEHAHN FKIYNSIKYK 

       310        320        330        340        350        360 
NHPEYQYLNI IYDIIMHGNK QDDRTGVGVL SKFGYMMKFN LNEYFPLLTT KKLFIRGIIE 

       370        380        390        400        410        420 
ELLWFIRGET NGNTLLEKNV RIWEANGTRE FLDNRKLFHR EVNDLGPIYG FQWRHFGAEY 

       430        440        450        460        470        480 
TDMHDNYKDK GVDQLKNIIN LIKNDPTCRR IILCAWNVKN LDQMALPPCH ILCQFYVFDG 

       490        500        510        520        530        540 
KLSCIMYQRS CDLGLGVPFN IASYSIFTYM IAQVCNLQAA EFIHVLGNAH VYNNHIESLK 

       550        560        570        580 
IQLNRTPYPF PTLKLNPDIK NIEDFTISDF TVQNYVHHDK INMDMAA

Q27713 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