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Protein

Bifunctional dihydrofolate reductase-thymidylate synthase 2

Gene

THY-2

Organism
Arabidopsis thaliana (Mouse-ear cress)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-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 (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 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

Complete GO annotation...

Keywords - Molecular functioni

Methyltransferase, Oxidoreductase, Transferase

Keywords - Biological processi

Nucleotide biosynthesis, One-carbon metabolism

Keywords - Ligandi

NADP

Enzyme and pathway databases

BioCyciARA:AT4G34570-MONOMER.
ReactomeiR-ATH-113510. E2F mediated regulation of DNA replication.
R-ATH-500753. Pyrimidine biosynthesis.
R-ATH-69205. G1/S-Specific Transcription.
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

TAIRiAT4G34570.

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

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.
OMAiNPVKKDI.
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.
InterProiIPR024072. DHFR-like_dom.
IPR012262. DHFR-TS.
IPR017925. DHFR_CS.
IPR001796. DHFR_dom.
IPR023451. Thymidate_synth/dCMP_Mease.
IPR000398. Thymidylate_synthase.
IPR020940. Thymidylate_synthase_AS.
[Graphical view]
PfamiPF00186. DHFR_1. 1 hit.
PF00303. Thymidylat_synt. 1 hit.
[Graphical view]
PIRSFiPIRSF000389. DHFR-TS. 1 hit.
PRINTSiPR00108. THYMDSNTHASE.
SUPFAMiSSF53597. SSF53597. 1 hit.
SSF55831. SSF55831. 1 hit.
TIGRFAMsiTIGR03284. thym_sym. 1 hit.
PROSITEiPS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
PS00091. THYMIDYLATE_SYNTHASE. 1 hit.
[Graphical view]

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_195183.2. NM_119623.5.
UniGeneiAt.31491.

Genome annotation databases

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

Cross-referencesi

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_195183.2. NM_119623.5.
UniGeneiAt.31491.

3D structure databases

ProteinModelPortaliQ05763.
SMRiQ05763.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi3702.AT4G34570.1.

Proteomic databases

PaxDbiQ05763.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

TAIRiAT4G34570.

Phylogenomic databases

eggNOGiKOG0673. Eukaryota.
KOG1324. Eukaryota.
COG0207. LUCA.
COG0262. LUCA.
HOGENOMiHOG000257901.
InParanoidiQ05763.
KOiK13998.
OMAiNPVKKDI.
OrthoDBiEOG093606BU.
PhylomeDBiQ05763.

Enzyme and pathway databases

UniPathwayiUPA00077; UER00158.
BioCyciARA:AT4G34570-MONOMER.
ReactomeiR-ATH-113510. E2F mediated regulation of DNA replication.
R-ATH-500753. Pyrimidine biosynthesis.
R-ATH-69205. G1/S-Specific Transcription.

Miscellaneous databases

PROiQ05763.

Gene expression databases

GenevisibleiQ05763. AT.

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.
InterProiIPR024072. DHFR-like_dom.
IPR012262. DHFR-TS.
IPR017925. DHFR_CS.
IPR001796. DHFR_dom.
IPR023451. Thymidate_synth/dCMP_Mease.
IPR000398. Thymidylate_synthase.
IPR020940. Thymidylate_synthase_AS.
[Graphical view]
PfamiPF00186. DHFR_1. 1 hit.
PF00303. Thymidylat_synt. 1 hit.
[Graphical view]
PIRSFiPIRSF000389. DHFR-TS. 1 hit.
PRINTSiPR00108. THYMDSNTHASE.
SUPFAMiSSF53597. SSF53597. 1 hit.
SSF55831. SSF55831. 1 hit.
TIGRFAMsiTIGR03284. thym_sym. 1 hit.
PROSITEiPS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
PS00091. THYMIDYLATE_SYNTHASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDRTS2_ARATH
AccessioniPrimary (citable) accession number: Q05763
Secondary accession number(s): Q0WT35
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: June 26, 2007
Last modified: November 30, 2016
This is version 132 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programPlant Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. Arabidopsis thaliana
    Arabidopsis thaliana: entries and gene names
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.