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Protein

Bifunctional dihydrofolate reductase-thymidylate synthase 1

Gene

THY-1

Organism
Arabidopsis thaliana (Mouse-ear cress)
Status
Reviewed-Annotation score: -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 (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 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

Keywordsi

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

Enzyme and pathway databases

BioCyciARA:AT2G16370-MONOMER
ReactomeiR-ATH-499943 Interconversion of nucleotide di- and triphosphates
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

AraportiAT2G16370
TAIRilocus:2042649 AT2G16370

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cell wall Cytoskeleton Vacuole Chloroplast Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertion Graphics by Christian Stolte; Source: COMPARTMENTS

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

ExpressionAtlasiQ05762 baseline and differential
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
OMAiVYSNHVE
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
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.

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
CP002685 Genomic DNA Translation: ANM62435.1
AY063968 mRNA Translation: AAL36324.1
AY114032 mRNA Translation: AAM45080.1
PIRiE84539
RefSeqiNP_001324593.1, NM_001335473.1
NP_179230.1, NM_127191.4
UniGeneiAt.27124

Genome annotation databases

EnsemblPlantsiAT2G16370.1; AT2G16370.1; AT2G16370
AT2G16370.3; AT2G16370.3; AT2G16370
GeneIDi816134
GrameneiAT2G16370.1; AT2G16370.1; AT2G16370
AT2G16370.3; AT2G16370.3; AT2G16370
KEGGiath:AT2G16370

Similar proteinsi

Entry informationi

Entry nameiDRTS1_ARATH
AccessioniPrimary (citable) accession number: Q05762
Secondary accession number(s): Q9SIW4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: May 27, 2002
Last modified: April 25, 2018
This is version 144 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
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Main funding by: National Institutes of Health