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Protein

Bifunctional dihydrofolate reductase-thymidylate synthase

Gene

LmjF06.0860

Organism
Leishmania major
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism. 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 (LmjF06.0860)
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 sitei30Substrate; via carbonyl oxygenBy similarity1
Binding sitei32NADP; via amide nitrogen and carbonyl oxygenBy similarity1
Binding sitei52SubstrateBy similarity1
Binding sitei162SubstrateBy similarity1
Binding sitei180SubstrateBy similarity1
Binding sitei254dUMPBy similarity1
Active sitei400By similarity1
Binding sitei401dUMPBy similarity1
Binding sitei433dUMPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi38 – 44NADPBy similarity7
Nucleotide bindingi81 – 83NADPBy similarity3
Nucleotide bindingi102 – 105NADPBy similarity4
Nucleotide bindingi157 – 164NADPBy similarity8
Nucleotide bindingi421 – 425dUMPBy similarity5
Nucleotide bindingi463 – 465dUMPBy 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)
Gene namesi
ORF Names:LmjF06.0860, LmjF_06_0860
OrganismiLeishmania major
Taxonomic identifieri5664 [NCBI]
Taxonomic lineageiEukaryotaEuglenozoaKinetoplastidaTrypanosomatidaeLeishmaniinaeLeishmania
Proteomesi
  • UP000000542 Componenti: Chromosome 6

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL4614.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001863451 – 520Bifunctional dihydrofolate reductase-thymidylate synthaseAdd BLAST520

Interactioni

Protein-protein interaction databases

STRINGi5664.LmjF.06.0860.

Chemistry databases

BindingDBiP07382.

Structurei

3D structure databases

ProteinModelPortaliP07382.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini26 – 229DHFRAdd BLAST204

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni234 – 520Thymidylate synthaseAdd BLAST287

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.
InParanoidiP07382.
KOiK13998.
OMAiNPVKKDI.

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.
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]
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.

P07382-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSRAAARFKI PMPETKADFA FPSLRAFSIV VALDMQHGIG DGESIPWRVP
60 70 80 90 100
EDMTFFKNQT TLLRNKKPPT EKKRNAVVMG RKTWESVPVK FRPLKGRLNI
110 120 130 140 150
VLSSKATVEE LLAPLPEGQR AAAAQDVVVV NGGLAEALRL LARPLYCSSI
160 170 180 190 200
ETAYCVGGAQ VYADAMLSPC IEKLQEVYLT RIYATAPACT RFFPFPPENA
210 220 230 240 250
ATAWDLASSQ GRRKSEAEGL EFEICKYVPR NHEERQYLEL IDRIMKTGIV
260 270 280 290 300
KEDRTGVGTI SLFGAQMRFS LRDNRLPLLT TKRVFWRGVC EELLWFLRGE
310 320 330 340 350
TSAQLLADKD IHIWDGNGSR EFLDSRGLTE NKEMDLGPVY GFQWRHFGAD
360 370 380 390 400
YKGFEANYDG EGVDQIKLIV ETIKTNPNDR RLLVTAWNPC ALQKMALPPC
410 420 430 440 450
HLLAQFYVNT DTSELSCMLY QRSCDMGLGV PFNIASYALL TILIAKATGL
460 470 480 490 500
RPGELVHTLG DAHVYRNHVD ALKAQLERVP HAFPTLIFKE ERQYLEDYEL
510 520
TDMEVIDYVP HPAIKMEMAV
Length:520
Mass (Da):58,689
Last modified:April 1, 1988 - v1
Checksum:i7D221F2CF2BE43D4
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti28S → C in AAA29272 (PubMed:3461439).Curated1
Sequence conflicti49V → S in AAA29272 (PubMed:3461439).Curated1
Sequence conflicti72 – 76KKRNA → EEAQR in AAA29272 (PubMed:3461439).Curated5
Sequence conflicti125 – 127QDV → RML in AAA29272 (PubMed:3461439).Curated3
Sequence conflicti307A → T in AAA29272 (PubMed:3461439).Curated1
Sequence conflicti397L → V in AAA29272 (PubMed:3461439).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M12734 Genomic DNA. Translation: AAA29232.1.
M14330 Genomic DNA. Translation: AAA29272.1.
X51733 Genomic DNA. Translation: CAA36019.1.
FR796402 Genomic DNA. Translation: CAJ02132.1.
PIRiA23403. RDLNTS.
RefSeqiXP_001680857.1. XM_001680805.1.

Genome annotation databases

GeneIDi5649109.
KEGGilma:LMJF_06_0860.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M12734 Genomic DNA. Translation: AAA29232.1.
M14330 Genomic DNA. Translation: AAA29272.1.
X51733 Genomic DNA. Translation: CAA36019.1.
FR796402 Genomic DNA. Translation: CAJ02132.1.
PIRiA23403. RDLNTS.
RefSeqiXP_001680857.1. XM_001680805.1.

3D structure databases

ProteinModelPortaliP07382.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi5664.LmjF.06.0860.

Chemistry databases

BindingDBiP07382.
ChEMBLiCHEMBL4614.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi5649109.
KEGGilma:LMJF_06_0860.

Phylogenomic databases

eggNOGiKOG0673. Eukaryota.
KOG1324. Eukaryota.
COG0207. LUCA.
COG0262. LUCA.
HOGENOMiHOG000257901.
InParanoidiP07382.
KOiK13998.
OMAiNPVKKDI.

Enzyme and pathway databases

UniPathwayiUPA00077; UER00158.

Miscellaneous databases

PROiP07382.

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.
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]
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_LEIMA
AccessioniPrimary (citable) accession number: P07382
Secondary accession number(s): Q4QIZ1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: April 1, 1988
Last modified: November 30, 2016
This is version 117 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Multifunctional enzyme, Reference proteome

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.