[1]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. PubMed=2601715 [NCBI, ExPASy, EBI, Israel, Japan] Cowman A.F., Lew A.M.; "Antifolate drug selection results in duplication and rearrangement of chromosome 7 in Plasmodium chabaudi."; Mol. Cell. Biol. 9:5182-5188(1989).
[2]	NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 12-193. 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

M30834; AAA29587.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
L28120; AAB59201.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

PIR

A33484; RDZQTB.

3D structure databases

HSSP

P13922; 1J3K. [HSSP ENTRY / PDB]

SMR

P20712; 260-583.

ModBase

P20712.

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

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

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 583`	`583`	`Bifunctional dihydrofolate reductase-thymidylate synthase.`	`PRO_0000186348`
`DOMAIN`	`9 229`	`221`	`DHFR.`
`REGION`	`298 583`	`286`	`Thymidylate synthase.`
`ACT_SITE`	`465 465`		`By similarity.`
`VARIANT`	`106 106`	`1`	`S -> I (in pyrimethamine resistance).`
`CONFLICT`	`27 27`		`G -> S (in Ref. 2; AAB59201).`
`CONFLICT`	`156 156`		`C -> S (in Ref. 2; AAB59201).`
`CONFLICT`	`164 164`		`I -> V (in Ref. 2; AAB59201).`

Sequence information

Length: 583 AA [This is the length of the unprocessed precursor]

Molecular weight: 68051 Da [This is the MW of the unprocessed precursor]

CRC64: 4AA55E1C987E6FD7 [This is a checksum on the sequence]

        10         20         30         40         50         60 
MEDISEIFDI YAICACCKVL NSNEKAGCFS NKTFKGLGNE GGLPWKCNSV DMKHFSSVTS 

        70         80         90        100        110        120 
YVNETNYMRL KWKRDRYMEK NNVKLNTDGI PSVDKLQNIV VMGKASWESI PSKFKPLQNR 

       130        140        150        160        170        180 
INIILSRTLK KEDLAKEYNN VIIINSVDDL FPILKCIKYY KCFIIGGASV YKEFLDRNLI 

       190        200        210        220        230        240 
KKIYFTRINN AYTCDVLFPD INEDLFKITS ISDVYSSNNT TLDFVIYSKT KEIHEEINPN 

       250        260        270        280        290        300 
DELFNNTFLG VCDEKNTNFD DEDDYTYFSF NKHKDNIKKN SEHAHHFKIY NSIKYKHHPE 

       310        320        330        340        350        360 
YQYLNIIYDI IMHGNKQDDR TGVGVLSKFG YMMKFNLSEY FPLLTTKKLF VRGIIEELLW 

       370        380        390        400        410        420 
FIRGETNGNT LLEKNVRIWE ANGTREFLDN RKLFHREVND LGPIYGFQWR HFGAEYTDMH 

       430        440        450        460        470        480 
ADYKDKGVDQ LKNIINLIKN DPTCRRIILC AWNVKDLDQM ALPPCHILCQ FYVFDGKLSC 

       490        500        510        520        530        540 
IMYQRSCDLG LGVPFNIASY SIFTYMIAQV CNLQPAEFIH VLGNAHVYNN HVESLKVQLN 

       550        560        570        580 
RTPYPFPTLK LNPEIKNIED FTISDFTVQN YVHHDKISMD MAA

P20712 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