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Protein

Bifunctional dihydrofolate reductase-thymidylate synthase 2

Gene

THY-2

Organism
Arabidopsis thaliana (Mouse-ear cress)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

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 activityi

5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH.
5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP.

Pathwayi: tetrahydrofolate biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate.
Proteins known to be involved in this subpathway in this organism are:
  1. Bifunctional dihydrofolate reductase-thymidylate synthase (AXX17_At2g11440), Bifunctional dihydrofolate reductase-thymidylate synthase (THY-2), Bifunctional dihydrofolate reductase-thymidylate synthase (THY-2), Bifunctional dihydrofolate reductase-thymidylate synthase (At2g21550), Bifunctional dihydrofolate reductase-thymidylate synthase (AXX17_At2g17080), Bifunctional dihydrofolate reductase-thymidylate synthase 1 (THY-1), Bifunctional dihydrofolate reductase-thymidylate synthase (AXX17_At4g39570), Bifunctional dihydrofolate reductase-thymidylate synthase (At2g21550), Bifunctional dihydrofolate reductase-thymidylate synthase 2 (THY-2)
This subpathway is part of the pathway tetrahydrofolate biosynthesis, which is itself part of Cofactor biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate, the pathway tetrahydrofolate biosynthesis and in Cofactor biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei69Substrate; via carbonyl oxygenBy similarity1
Binding sitei71NADP; via amide nitrogen and carbonyl oxygenBy similarity1
Binding sitei91SubstrateBy similarity1
Binding sitei178Substrate; via carbonyl oxygenBy similarity1
Binding sitei199SubstrateBy similarity1
Binding sitei302dUMPBy similarity1
Active sitei447By similarity1
Binding sitei448dUMPBy similarity1
Binding sitei478dUMPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi77 – 83NADPBy similarity7
Nucleotide bindingi115 – 117NADPBy similarity3
Nucleotide bindingi136 – 139NADPBy similarity4
Nucleotide bindingi179 – 186NADPBy similarity8
Nucleotide bindingi466 – 470dUMPBy similarity5
Nucleotide bindingi508 – 510dUMPBy similarity3

GO - Molecular functioni

  • dihydrofolate reductase activity Source: TAIR
  • thymidylate synthase activity Source: TAIR

GO - Biological processi

Keywordsi

Molecular functionMethyltransferase, Multifunctional enzyme, Oxidoreductase, Transferase
Biological processNucleotide biosynthesis, One-carbon metabolism
LigandNADP

Enzyme and pathway databases

BioCyciARA:AT4G34570-MONOMER
ReactomeiR-ATH-499943 Interconversion of nucleotide di- and triphosphates
UniPathwayiUPA00077; UER00158

Names & Taxonomyi

Protein namesi
Recommended name:
Bifunctional dihydrofolate reductase-thymidylate synthase 2
Short name:
DHFR-TS 2
Including the following 2 domains:
Dihydrofolate reductase (EC:1.5.1.3)
Thymidylate synthase (EC:2.1.1.45)
Gene namesi
Name:THY-2
Ordered Locus Names:At4g34570
ORF Names:T4L20.150
OrganismiArabidopsis thaliana (Mouse-ear cress)
Taxonomic identifieri3702 [NCBI]
Taxonomic lineageiEukaryotaViridiplantaeStreptophytaEmbryophytaTracheophytaSpermatophytaMagnoliophytaeudicotyledonsGunneridaePentapetalaerosidsmalvidsBrassicalesBrassicaceaeCamelineaeArabidopsis
Proteomesi
  • UP000006548 Componenti: Chromosome 4

Organism-specific databases

AraportiAT4G34570
TAIRilocus:2139544 AT4G34570

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001863561 – 565Bifunctional dihydrofolate reductase-thymidylate synthase 2Add BLAST565

Proteomic databases

PaxDbiQ05763

Expressioni

Gene expression databases

ExpressionAtlasiQ05763 baseline and differential
GenevisibleiQ05763 AT

Interactioni

Subunit structurei

Heterodimer or homodimer.By similarity

Protein-protein interaction databases

STRINGi3702.AT4G34570.1

Structurei

3D structure databases

ProteinModelPortaliQ05763
SMRiQ05763
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini65 – 242DHFRAdd BLAST178

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni245 – 280HingeAdd BLAST36
Regioni281 – 565Thymidylate synthaseAdd BLAST285

Sequence similaritiesi

In the N-terminal section; belongs to the dihydrofolate reductase family.Curated
In the C-terminal section; belongs to the thymidylate synthase family.Curated

Phylogenomic databases

eggNOGiKOG0673 Eukaryota
KOG1324 Eukaryota
COG0207 LUCA
COG0262 LUCA
HOGENOMiHOG000257901
InParanoidiQ05763
KOiK13998
OMAiICENGLR
OrthoDBiEOG093606BU
PhylomeDBiQ05763

Family and domain databases

CDDicd00209 DHFR, 1 hit
cd00351 TS_Pyrimidine_HMase, 1 hit
Gene3Di3.30.572.10, 1 hit
3.40.430.10, 1 hit
HAMAPiMF_00008 Thymidy_synth_bact, 1 hit
InterProiView protein in InterPro
IPR024072 DHFR-like_dom_sf
IPR012262 DHFR-TS
IPR017925 DHFR_CS
IPR001796 DHFR_dom
IPR023451 Thymidate_synth/dCMP_Mease
IPR036926 Thymidate_synth/dCMP_Mease_sf
IPR000398 Thymidylate_synthase
IPR020940 Thymidylate_synthase_AS
PANTHERiPTHR11548:SF7 PTHR11548:SF7, 1 hit
PfamiView protein in Pfam
PF00186 DHFR_1, 1 hit
PF00303 Thymidylat_synt, 1 hit
PIRSFiPIRSF000389 DHFR-TS, 1 hit
PRINTSiPR00108 THYMDSNTHASE
SUPFAMiSSF53597 SSF53597, 1 hit
SSF55831 SSF55831, 1 hit
TIGRFAMsiTIGR03284 thym_sym, 1 hit
PROSITEiView protein in PROSITE
PS00075 DHFR_1, 1 hit
PS51330 DHFR_2, 1 hit
PS00091 THYMIDYLATE_SYNTHASE, 1 hit

Sequencei

Sequence statusi: Complete.

Q05763-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRCLQNSAKT LPLAFKSALL PLSQRWFCKF SPKPSSLTNI FKVSISTMAN
60 70 80 90 100
TLNGNVIMTS KPQSTYQVVV AATKEMGIGK DGKLPWNLPT DLKFFKDLTL
110 120 130 140 150
STSDSAKKNA VVMGRKTWES IPKKYRPLSG RLNVVLSRSS GFDIANTENV
160 170 180 190 200
VTCSSIDSAL DLLAAPPFSL SIEKVFVIGG GDILREALNK PSCEAIHITE
210 220 230 240 250
IDTSIDCDTF IPTVDTSAYQ PWCSSFPICE NGLRFSFTTH VRVKSSSAGE
260 270 280 290 300
ASDESDGSKV LQVDWKKFSS VLPKMIFDRH EEYLYLNLVK EIISNGNLKD
310 320 330 340 350
DRTGTGTLSK FGCQMKFNLR RNFPLLTTKR VFWRGVVEEL LWFISGSTNA
360 370 380 390 400
KVLQEKGIRI WDGNASRAYL DGIGLTEREE GDLGPVYGFQ WRHFGAKYTD
410 420 430 440 450
MHADYTGQGF DQLLDVINKI KNNPDDRRII MSAWNPSDLK LMALPPCHMF
460 470 480 490 500
AQFYVANGEL SCQMYQRSAD MGLGVPFNIA SYSLLTCILA HVCDLVPGDF
510 520 530 540 550
IHVIGDAHVY KNHVRPLQEQ LENPPKPFPV LKINPEKKDI DSFVADDFEL
560
IGYDPHKKID MKMAV
Length:565
Mass (Da):63,209
Last modified:June 26, 2007 - v2
Checksum:iC442A1402A591DD9
GO

Sequence cautioni

The sequence AAA32789 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence CAA18836 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence CAB80174 differs from that shown. Reason: Erroneous gene model prediction.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L08594 Genomic DNA Translation: AAA32789.1 Sequence problems.
AL023094 Genomic DNA Translation: CAA18836.1 Sequence problems.
AL161585 Genomic DNA Translation: CAB80174.1 Sequence problems.
CP002687 Genomic DNA Translation: AEE86394.1
AK227728 mRNA Translation: BAE99713.1
BT003159 mRNA Translation: AAO24591.1
PIRiT05277
RefSeqiNP_001328948.1, NM_001342290.1
NP_001328950.1, NM_001342292.1
NP_195183.2, NM_119623.5
UniGeneiAt.31491

Genome annotation databases

EnsemblPlantsiAT4G34570.1; AT4G34570.1; AT4G34570
GeneIDi829609
GrameneiAT4G34570.1; AT4G34570.1; AT4G34570
KEGGiath:AT4G34570

Similar proteinsi

Entry informationi

Entry nameiDRTS2_ARATH
AccessioniPrimary (citable) accession number: Q05763
Secondary accession number(s): Q0WT35
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: June 26, 2007
Last modified: April 25, 2018
This is version 140 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programPlant Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health