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Protein

Dihydrofolate reductase

Gene

folA

Organism
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis (By similarity).By similarity

Catalytic activityi

5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH.PROSITE-ProRule annotation

Temperature dependencei

Highly thermostable.

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei7 – 71Substrate; via carbonyl oxygen
Binding sitei9 – 91NADP; via amide nitrogen and carbonyl oxygen1 Publication
Binding sitei16 – 161NADP; via carbonyl oxygen1 Publication
Binding sitei28 – 281Substrate
Binding sitei59 – 591SubstrateBy similarity
Binding sitei81 – 811NADP; via carbonyl oxygen1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi46 – 516NADP1 Publication
Nucleotide bindingi65 – 673NADP1 Publication
Nucleotide bindingi103 – 1053NADP1 Publication

GO - Molecular functioni

  1. dihydrofolate reductase activity Source: UniProtKB-EC
  2. NADP binding Source: InterPro

GO - Biological processi

  1. glycine biosynthetic process Source: InterPro
  2. nucleotide biosynthetic process Source: InterPro
  3. one-carbon metabolic process Source: UniProtKB-KW
  4. tetrahydrofolate biosynthetic process Source: UniProtKB-UniPathway
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

One-carbon metabolism

Keywords - Ligandi

NADP

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-461.
TMAR243274:GC6P-1687-MONOMER.
UniPathwayiUPA00077; UER00158.

Names & Taxonomyi

Protein namesi
Recommended name:
Dihydrofolate reductase (EC:1.5.1.3)
Short name:
DHFR
Gene namesi
Name:folA
Synonyms:dyrA
Ordered Locus Names:TM_1641
OrganismiThermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Taxonomic identifieri243274 [NCBI]
Taxonomic lineageiBacteriaThermotogaeThermotogalesThermotogaceaeThermotoga
ProteomesiUP000008183 Componenti: Chromosome

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 169169Dihydrofolate reductasePRO_0000186418Add
BLAST

Interactioni

Subunit structurei

Homodimer.1 Publication

Protein-protein interaction databases

STRINGi243274.TM1641.

Structurei

Secondary structure

1
169
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi3 – 108Combined sources
Beta strandi15 – 173Combined sources
Helixi26 – 3914Combined sources
Beta strandi41 – 455Combined sources
Helixi46 – 527Combined sources
Beta strandi59 – 646Combined sources
Beta strandi76 – 794Combined sources
Helixi83 – 9210Combined sources
Beta strandi96 – 1027Combined sources
Helixi104 – 1129Combined sources
Beta strandi117 – 1237Combined sources
Beta strandi125 – 1306Combined sources
Beta strandi132 – 1354Combined sources
Beta strandi141 – 15111Combined sources
Beta strandi153 – 1553Combined sources
Beta strandi158 – 1647Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1CZ3X-ray2.10A/B2-169[»]
1D1GX-ray2.10A/B2-169[»]
ProteinModelPortaliQ60034.
SMRiQ60034. Positions 2-169.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ60034.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini3 – 169167DHFRPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the dihydrofolate reductase family.Curated
Contains 1 DHFR (dihydrofolate reductase) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0262.
InParanoidiQ60034.
KOiK00287.
OMAiKGYERVA.
OrthoDBiEOG6KT2V2.

Family and domain databases

Gene3Di3.40.430.10. 1 hit.
InterProiIPR012259. DHFR.
IPR024072. DHFR-like_dom.
IPR001796. DHFR_dom.
[Graphical view]
PfamiPF00186. DHFR_1. 1 hit.
[Graphical view]
PRINTSiPR00070. DHFR.
SUPFAMiSSF53597. SSF53597. 1 hit.
PROSITEiPS51330. DHFR_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q60034-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAKVIFVLAM DVSGKIASSV ESWSSFEDRK NFRKITTEIG NVVMGRITFE
60 70 80 90 100
EIGRPLPERL NVVLTRRPKT SNNPSLVFFN GSPADVVKFL EGKGYERVAV
110 120 130 140 150
IGGKTVFTEF LREKLVDELF VTVEPYVFGK GIPFFDEFEG YFPLKLLEMR
160
RLNERGTLFL KYSVEKSHR
Length:169
Mass (Da):19,367
Last modified:November 1, 1997 - v1
Checksum:iF5DA22C978E2C39D
GO

Sequence cautioni

The sequence AAD36708.1 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti68 – 8114PKTSN…VFFNG → TQNFQQSFTRFFQR (PubMed:7789791).CuratedAdd
BLAST
Sequence conflicti108 – 1081T → S (PubMed:7789791).Curated
Sequence conflicti138 – 1392FE → LQ (PubMed:7789791).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X81845 Genomic DNA. Translation: CAA57437.1.
Y11021 Genomic DNA. Translation: CAA71903.1.
AE000512 Genomic DNA. Translation: AAD36708.1. Different initiation.
PIRiA72231.
RefSeqiNP_229441.1. NC_000853.1.
WP_004082129.1. NC_023151.1.
YP_007977999.1. NC_021214.1.

Genome annotation databases

EnsemblBacteriaiAAD36708; AAD36708; TM_1641.
GeneIDi896828.
KEGGitma:TM1641.
PATRICi23938256. VBITheMar51294_1660.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X81845 Genomic DNA. Translation: CAA57437.1.
Y11021 Genomic DNA. Translation: CAA71903.1.
AE000512 Genomic DNA. Translation: AAD36708.1. Different initiation.
PIRiA72231.
RefSeqiNP_229441.1. NC_000853.1.
WP_004082129.1. NC_023151.1.
YP_007977999.1. NC_021214.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1CZ3X-ray2.10A/B2-169[»]
1D1GX-ray2.10A/B2-169[»]
ProteinModelPortaliQ60034.
SMRiQ60034. Positions 2-169.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi243274.TM1641.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiAAD36708; AAD36708; TM_1641.
GeneIDi896828.
KEGGitma:TM1641.
PATRICi23938256. VBITheMar51294_1660.

Phylogenomic databases

eggNOGiCOG0262.
InParanoidiQ60034.
KOiK00287.
OMAiKGYERVA.
OrthoDBiEOG6KT2V2.

Enzyme and pathway databases

UniPathwayiUPA00077; UER00158.
BioCyciMetaCyc:MONOMER-461.
TMAR243274:GC6P-1687-MONOMER.

Miscellaneous databases

EvolutionaryTraceiQ60034.

Family and domain databases

Gene3Di3.40.430.10. 1 hit.
InterProiIPR012259. DHFR.
IPR024072. DHFR-like_dom.
IPR001796. DHFR_dom.
[Graphical view]
PfamiPF00186. DHFR_1. 1 hit.
[Graphical view]
PRINTSiPR00070. DHFR.
SUPFAMiSSF53597. SSF53597. 1 hit.
PROSITEiPS51330. DHFR_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The dihydrofolate reductase-encoding gene dyrA of the hyperthermophilic bacterium Thermotoga maritima."
    van de Casteele M., Legrain C., Wilquet V., Glansdorff N.
    Gene 158:101-105(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "Homo-dimeric recombinant dihydrofolate reductase from Thermotoga maritima shows extreme intrinsic stability."
    Dams T., Schurig H., Jaenicke R.
    Biol. Chem. 379:367-371(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: ATCC 43589 / MSB8 / DSM 3109 / JCM 10099.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: ATCC 43589 / MSB8 / DSM 3109 / JCM 10099.
  4. "The crystal structure of dihydrofolate reductase from Thermotoga maritima: molecular features of thermostability."
    Dams T., Auerbach G., Bader G., Jacob U., Ploom T., Huber R., Jaenicke R.
    J. Mol. Biol. 297:659-672(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH METHOTREXATE AND NADPH.

Entry informationi

Entry nameiDYR_THEMA
AccessioniPrimary (citable) accession number: Q60034
Secondary accession number(s): P96109
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: April 29, 2015
This is version 113 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.