Reviewed, UniProtKB/Swiss-Prot Q05763 (DRTS2_ARATH)

Names and origin

Protein names

Recommended name:
    Bifunctional dihydrofolate reductase-thymidylate synthase 2
      Short name=DHFR-TS 2
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-2
Ordered Locus Names:	At4g34570
ORF Names:	T4L20.150

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	565 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.
Sequence caution	The sequence AAA32789.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAA18836.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAB80174.1 differs from that shown. Reason: Erroneous gene model prediction.

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 – 565	565	Bifunctional dihydrofolate reductase-thymidylate synthase 2		PRO_0000186356
Regions
	Domain	65 – 242	178	DHFR
	Nucleotide binding	77 – 83	7	NADP By similarity
	Nucleotide binding	115 – 117	3	NADP By similarity
	Nucleotide binding	136 – 139	4	NADP By similarity
	Nucleotide binding	179 – 186	8	NADP By similarity
	Nucleotide binding	466 – 470	5	dUMP By similarity
	Nucleotide binding	508 – 510	3	dUMP By similarity
	Region	245 – 280	36	Hinge
	Region	281 – 565	285	Thymidylate synthase
Sites
	Active site	447	1	By similarity
	Binding site	69	1	Substrate; via carbonyl oxygen By similarity
	Binding site	71	1	NADP; via amide nitrogen and carbonyl oxygen By similarity
	Binding site	91	1	Substrate By similarity
	Binding site	178	1	Substrate; via carbonyl oxygen By similarity
	Binding site	199	1	Substrate By similarity
	Binding site	302	1	dUMP By similarity
	Binding site	448	1	dUMP By similarity
	Binding site	478	1	dUMP By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q05763-1 [UniParc]. Last modified June 26, 2007. Version 2. Checksum: C442A1402A591DD9	FASTA	565	63,209
	10 20 30 40 50 60 MRCLQNSAKT LPLAFKSALL PLSQRWFCKF SPKPSSLTNI FKVSISTMAN TLNGNVIMTS 70 80 90 100 110 120 KPQSTYQVVV AATKEMGIGK DGKLPWNLPT DLKFFKDLTL STSDSAKKNA VVMGRKTWES 130 140 150 160 170 180 IPKKYRPLSG RLNVVLSRSS GFDIANTENV VTCSSIDSAL DLLAAPPFSL SIEKVFVIGG 190 200 210 220 230 240 GDILREALNK PSCEAIHITE IDTSIDCDTF IPTVDTSAYQ PWCSSFPICE NGLRFSFTTH 250 260 270 280 290 300 VRVKSSSAGE ASDESDGSKV LQVDWKKFSS VLPKMIFDRH EEYLYLNLVK EIISNGNLKD 310 320 330 340 350 360 DRTGTGTLSK FGCQMKFNLR RNFPLLTTKR VFWRGVVEEL LWFISGSTNA KVLQEKGIRI 370 380 390 400 410 420 WDGNASRAYL DGIGLTEREE GDLGPVYGFQ WRHFGAKYTD MHADYTGQGF DQLLDVINKI 430 440 450 460 470 480 KNNPDDRRII MSAWNPSDLK LMALPPCHMF AQFYVANGEL SCQMYQRSAD MGLGVPFNIA 490 500 510 520 530 540 SYSLLTCILA HVCDLVPGDF IHVIGDAHVY KNHVRPLQEQ LENPPKPFPV LKINPEKKDI 550 560 DSFVADDFEL IGYDPHKKID MKMAV

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 4 of the plant Arabidopsis thaliana." Mayer K.F.X., Schueller C., Wambutt R., Murphy G., Volckaert G., Pohl T., Duesterhoeft A., Stiekema W., Entian K.-D., Terryn N., Harris B., Ansorge W., Brandt P., Grivell L.A., Rieger M., Weichselgartner M., de Simone V., Obermaier B. , Mache R., Mueller M., Kreis M., Delseny M., Puigdomenech P., Watson M., Schmidtheini T., Reichert B., Portetelle D., Perez-Alonso M., Boutry M., Bancroft I., Vos P., Hoheisel J., Zimmermann W., Wedler H., Ridley P., Langham S.-A., McCullagh B., Bilham L., Robben J., van der Schueren J., Grymonprez B., Chuang Y.-J., Vandenbussche F., Braeken M., Weltjens I., Voet M., Bastiaens I., Aert R., Defoor E., Weitzenegger T., Bothe G., Ramsperger U., Hilbert H., Braun M., Holzer E., Brandt A., Peters S., van Staveren M., Dirkse W., Mooijman P., Klein Lankhorst R., Rose M., Hauf J., Koetter P., Berneiser S., Hempel S., Feldpausch M., Lamberth S., Van den Daele H., De Keyser A., Buysshaert C., Gielen J., Villarroel R., De Clercq R., van Montagu M., Rogers J., Cronin A., Quail M.A., Bray-Allen S., Clark L., Doggett J., Hall S., Kay M., Lennard N., McLay K., Mayes R., Pettett A., Rajandream M.A., Lyne M., Benes V., Rechmann S., Borkova D., Bloecker H., Scharfe M., Grimm M., Loehnert T.-H., Dose S., de Haan M., Maarse A.C., Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Fartmann B., Granderath K., Dauner D., Herzl A., Neumann S., Argiriou A., Vitale D., Liguori R., Piravandi E., Massenet O., Quigley F., Clabauld G., Muendlein A., Felber R., Schnabl S., Hiller R., Schmidt W., Lecharny A., Aubourg S., Chefdor F., Cooke R., Berger C., Monfort A., Casacuberta E., Gibbons T., Weber N., Vandenbol M., Bargues M., Terol J., Torres A., Perez-Perez A., Purnelle B., Bent E., Johnson S., Tacon D., Jesse T., Heijnen L., Schwarz S., Scholler P., Heber S., Francs P., Bielke C., Frishman D., Haase D., Lemcke K., Mewes H.-W., Stocker S., Zaccaria P., Bevan M., Wilson R.K., de la Bastide M., Habermann K., Parnell L., Dedhia N., Gnoj L., Schutz K., Huang E., Spiegel L., Sekhon M., Murray J., Sheet P., Cordes M., Abu-Threideh J., Stoneking T., Kalicki J., Graves T., Harmon G., Edwards J., Latreille P., Courtney L., Cloud J., Abbott A., Scott K., Johnson D., Minx P., Bentley D., Fulton B., Miller N., Greco T., Kemp K., Kramer J., Fulton L., Mardis E., Dante M., Pepin K., Hillier L.W., Nelson J., Spieth J., Ryan E., Andrews S., Geisel C., Layman D., Du H., Ali J., Berghoff A., Jones K., Drone K., Cotton M., Joshu C., Antonoiu B., Zidanic M., Strong C., Sun H., Lamar B., Yordan C., Ma P., Zhong J., Preston R., Vil D., Shekher M., Matero A., Shah R., Swaby I.K., O'Shaughnessy A., Rodriguez M., Hoffman J., Till S., Granat S., Shohdy N., Hasegawa A., Hameed A., Lodhi M., Johnson A., Chen E., Marra M.A., Martienssen R., McCombie W.R. Nature 402:769-777(1999) [PubMed: 10617198] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: cv. Columbia.
[3]	"Large-scale analysis of RIKEN Arabidopsis full-length (RAFL) cDNAs." Totoki Y., Seki M., Ishida J., Nakajima M., Enju A., Kamiya A., Narusaka M., Shin-i T., Nakagawa M., Sakamoto N., Oishi K., Kohara Y., Kobayashi M., Toyoda A., Sakaki Y., Sakurai T., Iida K., Akiyama K. , Satou M., Toyoda T., Konagaya A., Carninci P., Kawai J., Hayashizaki Y., Shinozaki K. Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: cv. Columbia.
[4]	"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] OF 48-565. Strain: cv. Columbia.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L08594 Genomic DNA. Translation: AAA32789.1. Sequence problems. AL023094 Genomic DNA. Translation: CAA18836.1. Sequence problems. AL161585 Genomic DNA. Translation: CAB80174.1. Sequence problems. AK227728 mRNA. Translation: BAE99713.1. BT003159 mRNA. Translation: AAO24591.1.
IPI	IPI00526255.
PIR	T05277.
RefSeq	NP_195183.2.
UniGene	At.31491
3D structure databases
SMR	Q05763. Positions 50-559, 229-565.
ModBase	Search...
Protein-protein interaction databases
STRING	Q05763.
Genome annotation databases
GeneID	829609.
GenomeReviews	Gene locus AT4G34570 in contig CT486007_GR.
KEGG	ath:AT4G34570.
NMPDR	fig|3702.1.peg.21530.
Organism-specific databases
TAIR	At4g34570.
Phylogenomic databases
eggNOG	KOG0673.
HOGENOM	HBG588098.
InParanoid	Q05763.
OMA	WESIPKK.
PhylomeDB	Q05763.
Enzyme and pathway databases
BRENDA	1.5.1.3. 302. 2.1.1.45. 302.
Gene expression databases
ArrayExpress	Q05763.
Genevestigator	Q05763.
GermOnline	AT4G34570. 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

DRTS2_ARATH

Accession

Primary (citable) accession number: Q05763
Secondary accession number(s): Q0WT35

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	June 26, 2007
Last modified:	February 9, 2010
This is version 83 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

PPAP (Plant Proteome Annotation Project)