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Protein

Bifunctional dihydrofolate reductase-thymidylate synthase 1

Gene

THY-1

Organism
Arabidopsis thaliana (Mouse-ear cress)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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 sitei25Substrate; via carbonyl oxygenBy similarity1
Binding sitei27NADP; via amide nitrogen and carbonyl oxygenBy similarity1
Binding sitei47SubstrateBy similarity1
Binding sitei134Substrate; via carbonyl oxygenBy similarity1
Binding sitei155SubstrateBy similarity1
Binding sitei256dUMPBy similarity1
Active sitei401By similarity1
Binding sitei402dUMPBy similarity1
Binding sitei432dUMPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi33 – 39NADPBy similarity7
Nucleotide bindingi71 – 73NADPBy similarity3
Nucleotide bindingi92 – 95NADPBy similarity4
Nucleotide bindingi135 – 142NADPBy similarity8
Nucleotide bindingi420 – 424dUMPBy similarity5
Nucleotide bindingi462 – 464dUMPBy 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:AT2G16370-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 1
Short name:
DHFR-TS 1
Including the following 2 domains:
Dihydrofolate reductase (EC:1.5.1.3)
Thymidylate synthase (EC:2.1.1.45)
Gene namesi
Name:THY-1
Ordered Locus Names:At2g16370
ORF Names:F16F14.13
OrganismiArabidopsis thaliana (Mouse-ear cress)
Taxonomic identifieri3702 [NCBI]
Taxonomic lineageiEukaryotaViridiplantaeStreptophytaEmbryophytaTracheophytaSpermatophytaMagnoliophytaeudicotyledonsGunneridaePentapetalaerosidsmalvidsBrassicalesBrassicaceaeCamelineaeArabidopsis
Proteomesi
  • UP000006548 Componenti: Chromosome 2

Organism-specific databases

TAIRiAT2G16370.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: TAIR
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001863552 – 519Bifunctional dihydrofolate reductase-thymidylate synthase 1Add BLAST518

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

PaxDbiQ05762.

PTM databases

iPTMnetiQ05762.

Expressioni

Gene expression databases

GenevisibleiQ05762. AT.

Interactioni

Subunit structurei

Heterodimer or homodimer.By similarity

Protein-protein interaction databases

BioGridi1492. 2 interactors.
IntActiQ05762. 1 interactor.
STRINGi3702.AT2G16370.1.

Structurei

3D structure databases

ProteinModelPortaliQ05762.
SMRiQ05762.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini21 – 198DHFRAdd BLAST178

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni201 – 234HingeAdd BLAST34
Regioni235 – 519Thymidylate 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

eggNOGiENOG410JUW5. Eukaryota.
KOG0673. Eukaryota.
KOG1324. Eukaryota.
COG0207. LUCA.
COG0262. LUCA.
HOGENOMiHOG000257901.
InParanoidiQ05762.
KOiK13998.
OMAiFDQHEEF.
OrthoDBiEOG093606BU.
PhylomeDBiQ05762.

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.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q05762-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATTTLNDSV TTTLASEPQR TYQVVVAATK EMGIGKDGKL PWNLPTDLKF
60 70 80 90 100
FKDITLTTSD SSKKNAVVMG RKTWESIPIK YRPLSGRLNV VLTRSGGFDI
110 120 130 140 150
ANTENVVTCS SVDSALDLLA APPYCLSIER VFVIGGGDIL REALNRPSCD
160 170 180 190 200
AIHLTEIDTS VDCDTFIPAI DTSVYQPWSS SFPVTENGLR FCFTTFVRVK
210 220 230 240 250
SSADESSDES NGSQSLQFDG KKFLFLPKMV FDQHEEFLYL NMVEDIISNG
260 270 280 290 300
NVKNDRTGTG TLSKFGCQMK FNLRRSFPLL TTKRVFWRGV VEELLWFISG
310 320 330 340 350
STNAKVLQEK GIHIWDGNAS REYLDGIGLT EREEGDLGPV YGFQWRHFGA
360 370 380 390 400
KYTDMHADYT GQGFDQLVDV IDKIKNNPDD RRIIMSAWNP SDLKLMALPP
410 420 430 440 450
CHMFAQFYVA EGELSCQMYQ RSADMGLGVP FNIASYSLLT CMLAHVCDLV
460 470 480 490 500
PGDFIHVLGD AHVYKTHVRP LQEQLLNLPK PFPVMKINPE KKQIDSFVAS
510
DFDLTGYDPH KKIEMKMAV
Length:519
Mass (Da):58,143
Last modified:May 27, 2002 - v2
Checksum:iB5EB36A3A936580F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti120A → R in AAA32788 (PubMed:8374616).Curated1
Sequence conflicti478L → P in AAA32788 (PubMed:8374616).Curated1
Sequence conflicti485M → L in AAA32788 (PubMed:8374616).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L08593 mRNA. Translation: AAA32788.1.
AC007047 Genomic DNA. Translation: AAD22302.1.
CP002685 Genomic DNA. Translation: AEC06489.1.
AY063968 mRNA. Translation: AAL36324.1.
AY114032 mRNA. Translation: AAM45080.1.
PIRiE84539.
RefSeqiNP_179230.1. NM_127191.4.
UniGeneiAt.27124.

Genome annotation databases

EnsemblPlantsiAT2G16370.1; AT2G16370.1; AT2G16370.
GeneIDi816134.
GrameneiAT2G16370.1; AT2G16370.1; AT2G16370.
KEGGiath:AT2G16370.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L08593 mRNA. Translation: AAA32788.1.
AC007047 Genomic DNA. Translation: AAD22302.1.
CP002685 Genomic DNA. Translation: AEC06489.1.
AY063968 mRNA. Translation: AAL36324.1.
AY114032 mRNA. Translation: AAM45080.1.
PIRiE84539.
RefSeqiNP_179230.1. NM_127191.4.
UniGeneiAt.27124.

3D structure databases

ProteinModelPortaliQ05762.
SMRiQ05762.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi1492. 2 interactors.
IntActiQ05762. 1 interactor.
STRINGi3702.AT2G16370.1.

PTM databases

iPTMnetiQ05762.

Proteomic databases

PaxDbiQ05762.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblPlantsiAT2G16370.1; AT2G16370.1; AT2G16370.
GeneIDi816134.
GrameneiAT2G16370.1; AT2G16370.1; AT2G16370.
KEGGiath:AT2G16370.

Organism-specific databases

TAIRiAT2G16370.

Phylogenomic databases

eggNOGiENOG410JUW5. Eukaryota.
KOG0673. Eukaryota.
KOG1324. Eukaryota.
COG0207. LUCA.
COG0262. LUCA.
HOGENOMiHOG000257901.
InParanoidiQ05762.
KOiK13998.
OMAiFDQHEEF.
OrthoDBiEOG093606BU.
PhylomeDBiQ05762.

Enzyme and pathway databases

UniPathwayiUPA00077; UER00158.
BioCyciARA:AT2G16370-MONOMER.
ReactomeiR-ATH-113510. E2F mediated regulation of DNA replication.
R-ATH-500753. Pyrimidine biosynthesis.
R-ATH-69205. G1/S-Specific Transcription.

Miscellaneous databases

PROiQ05762.

Gene expression databases

GenevisibleiQ05762. 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 nameiDRTS1_ARATH
AccessioniPrimary (citable) accession number: Q05762
Secondary accession number(s): Q9SIW4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: May 27, 2002
Last modified: November 30, 2016
This is version 136 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.