Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Bifunctional dihydrofolate reductase-thymidylate synthase

Gene
N/A
Organism
Daucus carota (Wild carrot)
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 (By similarity).By similarity

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, Bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS)
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 sitei27Substrate; via carbonyl oxygenBy similarity1
Binding sitei29NADP; via amide nitrogen and carbonyl oxygenBy similarity1
Binding sitei49SubstrateBy similarity1
Binding sitei136Substrate; via carbonyl oxygenBy similarity1
Binding sitei142SubstrateBy similarity1
Binding sitei157SubstrateBy similarity1
Binding sitei264dUMPBy similarity1
Active sitei409By similarity1
Binding sitei410dUMPBy similarity1
Binding sitei440dUMPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi35 – 41NADPBy similarity7
Nucleotide bindingi73 – 75NADPBy similarity3
Nucleotide bindingi94 – 97NADPBy similarity4
Nucleotide bindingi137 – 144NADPBy similarity8
Nucleotide bindingi428 – 432dUMPBy similarity5
Nucleotide bindingi470 – 472dUMPBy similarity3

GO - Molecular functioni

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

UniPathwayiUPA00077; UER00158.

Names & Taxonomyi

Protein namesi
Recommended name:
Bifunctional dihydrofolate reductase-thymidylate synthase
Short name:
DHFR-TS
Including the following 2 domains:
Dihydrofolate reductase (EC:1.5.1.3)
Thymidylate synthase (EC:2.1.1.45)
OrganismiDaucus carota (Wild carrot)
Taxonomic identifieri4039 [NCBI]
Taxonomic lineageiEukaryotaViridiplantaeStreptophytaEmbryophytaTracheophytaSpermatophytaMagnoliophytaeudicotyledonsGunneridaePentapetalaeasteridscampanulidsApialesApiaceaeApioideaeScandiceaeDaucinaeDaucusDaucus sect. Daucus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001863571 – 528Bifunctional dihydrofolate reductase-thymidylate synthaseAdd BLAST528

Structurei

3D structure databases

ProteinModelPortaliP45350.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini23 – 200DHFRAdd BLAST178

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni202 – 528Thymidylate synthaseAdd BLAST327

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

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.

P45350-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASELLANPT NGSGITRPDP QRTYQVVVAA TQNMGIGKDG KLPWRLPSDM
60 70 80 90 100
KFFKDVTMTT SDPLKRNAVI MGRKTWESIP IQHRPLPGRL NVVLTRSGSF
110 120 130 140 150
DIATVENVVI CGSMISALEL LAGSPYCVSV EKVFVIGGGQ IYREALNAPG
160 170 180 190 200
CDAVHITEIE EHIECDTFIP LLDESVFQPW YSSFPLVENK IRYCFTTYVR
210 220 230 240 250
VRNSVAELTS QTNGCSSDSK SDSGNFEIQN FSFLPKTVFE KHEEYLYLGL
260 270 280 290 300
VENIISNGVT KNDRTRTGTV SIFGCQMRFN LRKSFPLLTT KKVFWRGVVE
310 320 330 340 350
ELLWFISGST NAKILKEKGV NIWEGNGSRE YLDSIGLTDR EEGDLGPIYG
360 370 380 390 400
FQWRHFGARY TDMHADYSGQ GFDQLLDVIS KIKNNPDDRR IIQSAWNPSD
410 420 430 440 450
LRLMALPPCH MFAQFYVANG ELSCQMYQRS ADMGLGVPFN IAAYALLTCM
460 470 480 490 500
IAHVCDLVPG DFVHSIGDAH VYSNHLSDLF ETSFRMLPKT FPVLKINSGE
510 520
KDIDSFEAAD FKLIGYDPHQ KIEMKMAV
Length:528
Mass (Da):59,259
Last modified:November 1, 1995 - v1
Checksum:i8BE07C221A546A56
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z17306 mRNA. Translation: CAA78954.1.
PIRiS35272.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z17306 mRNA. Translation: CAA78954.1.
PIRiS35272.

3D structure databases

ProteinModelPortaliP45350.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Enzyme and pathway databases

UniPathwayiUPA00077; UER00158.

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 nameiDRTS_DAUCA
AccessioniPrimary (citable) accession number: P45350
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: November 30, 2016
This is version 84 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programPlant Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Multifunctional enzyme

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. 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.