Reviewed, UniProtKB/Swiss-Prot Q05762 (DRTS1_ARATH)

Names and origin

Protein names

Recommended name:
    Bifunctional dihydrofolate reductase-thymidylate synthase 1
      Short name=DHFR-TS 1
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

Gene names

Name:	THY-1
Ordered Locus Names:	At2g16370
ORF Names:	F16F14.13

Organism

Arabidopsis thaliana (Mouse-ear cress) [Complete proteome]

Taxonomic identifier

3702 [NCBI]

Taxonomic lineage

Eukaryota › Viridiplantae › Streptophyta › Embryophyta › Tracheophyta › Spermatophyta › Magnoliophyta › eudicotyledons › core eudicotyledons › rosids › malvids › Brassicales › Brassicaceae › Arabidopsis

Protein attributes

Sequence length	519 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism. Can play two different roles depending on the source of dihydrofolate: de novo synthesis of tetrahydrofolate or recycling of the dihydrofolate released as one of the end products of the TS catalyzed reaction. Catalyzes an essential reaction for de novo glycine and purine synthesis, DNA precursor synthesis, and for the conversion of dUMP to dTMP.
Catalytic activity	5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH. 5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP.
Pathway	Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate: step 1/1.
Subunit structure	Heterodimer or homodimer By similarity.
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	Complete proteome 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 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 – 519	519	Bifunctional dihydrofolate reductase-thymidylate synthase 1		PRO_0000186355
Regions
	Domain	21 – 198	178	DHFR
	Nucleotide binding	33 – 39	7	NADP By similarity
	Nucleotide binding	71 – 73	3	NADP By similarity
	Nucleotide binding	92 – 95	4	NADP By similarity
	Nucleotide binding	135 – 142	8	NADP By similarity
	Nucleotide binding	420 – 424	5	dUMP By similarity
	Nucleotide binding	462 – 464	3	dUMP By similarity
	Region	201 – 234	34	Hinge
	Region	235 – 519	285	Thymidylate synthase
Sites
	Active site	401	1	By similarity
	Binding site	25	1	Substrate; via carbonyl oxygen By similarity
	Binding site	27	1	NADP; via amide nitrogen and carbonyl oxygen By similarity
	Binding site	47	1	Substrate By similarity
	Binding site	134	1	Substrate; via carbonyl oxygen By similarity
	Binding site	155	1	Substrate By similarity
	Binding site	256	1	dUMP By similarity
	Binding site	402	1	dUMP By similarity
	Binding site	432	1	dUMP By similarity
Experimental info
	Sequence conflict	120	1	A → R in AAA32788. Ref.1
	Sequence conflict	478	1	L → P in AAA32788. Ref.1
	Sequence conflict	485	1	M → L in AAA32788. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q05762-1 [UniParc]. Last modified May 27, 2002. Version 2. Checksum: B5EB36A3A936580F	FASTA	519	58,143
	10 20 30 40 50 60 MATTTLNDSV TTTLASEPQR TYQVVVAATK EMGIGKDGKL PWNLPTDLKF FKDITLTTSD 70 80 90 100 110 120 SSKKNAVVMG RKTWESIPIK YRPLSGRLNV VLTRSGGFDI ANTENVVTCS SVDSALDLLA 130 140 150 160 170 180 APPYCLSIER VFVIGGGDIL REALNRPSCD AIHLTEIDTS VDCDTFIPAI DTSVYQPWSS 190 200 210 220 230 240 SFPVTENGLR FCFTTFVRVK SSADESSDES NGSQSLQFDG KKFLFLPKMV FDQHEEFLYL 250 260 270 280 290 300 NMVEDIISNG NVKNDRTGTG TLSKFGCQMK FNLRRSFPLL TTKRVFWRGV VEELLWFISG 310 320 330 340 350 360 STNAKVLQEK GIHIWDGNAS REYLDGIGLT EREEGDLGPV YGFQWRHFGA KYTDMHADYT 370 380 390 400 410 420 GQGFDQLVDV IDKIKNNPDD RRIIMSAWNP SDLKLMALPP CHMFAQFYVA EGELSCQMYQ 430 440 450 460 470 480 RSADMGLGVP FNIASYSLLT CMLAHVCDLV PGDFIHVLGD AHVYKTHVRP LQEQLLNLPK 490 500 510 PFPVMKINPE KKQIDSFVAS DFDLTGYDPH KKIEMKMAV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The origin of the bifunctional dihydrofolate reductase-thymidylate synthase isogenes of Arabidopsis thaliana." Lazar G., Zhang H., Goodman H.M. Plant J. 3:657-668(1993) [PubMed: 8374616] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: cv. Landsberg erecta.
[2]	"Sequence and analysis of chromosome 2 of the plant Arabidopsis thaliana." Lin X., Kaul S., Rounsley S.D., Shea T.P., Benito M.-I., Town C.D., Fujii C.Y., Mason T.M., Bowman C.L., Barnstead M.E., Feldblyum T.V., Buell C.R., Ketchum K.A., Lee J.J., Ronning C.M., Koo H.L., Moffat K.S., Cronin L.A. , Shen M., Pai G., Van Aken S., Umayam L., Tallon L.J., Gill J.E., Adams M.D., Carrera A.J., Creasy T.H., Goodman H.M., Somerville C.R., Copenhaver G.P., Preuss D., Nierman W.C., White O., Eisen J.A., Salzberg S.L., Fraser C.M., Venter J.C. Nature 402:761-768(1999) [PubMed: 10617197] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: cv. Columbia.
[3]	"Empirical analysis of transcriptional activity in the Arabidopsis genome." Yamada K., Lim J., Dale J.M., Chen H., Shinn P., Palm C.J., Southwick A.M., Wu H.C., Kim C.J., Nguyen M., Pham P.K., Cheuk R.F., Karlin-Newmann G., Liu S.X., Lam B., Sakano H., Wu T., Yu G. , Miranda M., Quach H.L., Tripp M., Chang C.H., Lee J.M., Toriumi M.J., Chan M.M., Tang C.C., Onodera C.S., Deng J.M., Akiyama K., Ansari Y., Arakawa T., Banh J., Banno F., Bowser L., Brooks S.Y., Carninci P., Chao Q., Choy N., Enju A., Goldsmith A.D., Gurjal M., Hansen N.F., Hayashizaki Y., Johnson-Hopson C., Hsuan V.W., Iida K., Karnes M., Khan S., Koesema E., Ishida J., Jiang P.X., Jones T., Kawai J., Kamiya A., Meyers C., Nakajima M., Narusaka M., Seki M., Sakurai T., Satou M., Tamse R., Vaysberg M., Wallender E.K., Wong C., Yamamura Y., Yuan S., Shinozaki K., Davis R.W., Theologis A., Ecker J.R. Science 302:842-846(2003) [PubMed: 14593172] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: cv. Columbia.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L08593 mRNA. Translation: AAA32788.1. AC007047 Genomic DNA. Translation: AAD22302.1. AY063968 mRNA. Translation: AAL36324.1. AY114032 mRNA. Translation: AAM45080.1.
IPI	IPI00530946.
PIR	E84539.
RefSeq	NP_179230.1.
UniGene	At.27124
3D structure databases
SMR	Q05762. Positions 17-513, 234-519.
ModBase	Search...
Protein-protein interaction databases
STRING	Q05762.
Proteomic databases
PRIDE	Q05762.
Genome annotation databases
GeneID	816134.
GenomeReviews	Gene locus AT2G16370 in contig CT485783_GR.
KEGG	ath:AT2G16370.
NMPDR	fig|3702.1.peg.8626.
Organism-specific databases
TAIR	At2g16370.
Phylogenomic databases
eggNOG	KOG0673.
HOGENOM	HBG588098.
InParanoid	Q05762.
OMA	HADYTGK.
PhylomeDB	Q05762.
Enzyme and pathway databases
BRENDA	1.5.1.3. 302. 2.1.1.45. 302.
Gene expression databases
ArrayExpress	Q05762.
Genevestigator	Q05762.
GermOnline	AT2G16370. Arabidopsis thaliana.
Family and domain databases
InterPro	IPR012262. DHFR-TS. IPR017925. Dihydrofolate_reductase_CS. IPR001796. Dihydrofolate_reductase_dom. IPR000398. Thymidylate_synthase. IPR020940. Thymidylate_synthase_AS. [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.
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

DRTS1_ARATH

Accession

Primary (citable) accession number: Q05762
Secondary accession number(s): Q9SIW4

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	May 27, 2002
Last modified:	February 9, 2010
This is version 85 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

PPAP (Plant Proteome Annotation Project)