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Protein

Bifunctional dihydrofolate reductase-thymidylate synthase

Gene
N/A
Organism
Daucus carota (Wild carrot)
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 (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

Keywordsi

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

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
SMRiP45350
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
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.

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

Similar proteinsi

Entry informationi

Entry nameiDRTS_DAUCA
AccessioniPrimary (citable) accession number: P45350
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: February 28, 2018
This is version 90 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programPlant Protein Annotation Program

Miscellaneousi

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

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