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Protein

Dihydrofolate reductase type 1 from Tn4003

Gene

dfrA

Organism
Staphylococcus aureus
Status
Reviewed-Annotation score: Annotation score: 5 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.

Catalytic activityi

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

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei28 – 281Substrate
Binding sitei58 – 581Substrate
Binding sitei112 – 1121Substrate

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi7 – 82NADP1 Publication
Nucleotide bindingi15 – 206NADP1 Publication
Nucleotide bindingi44 – 474NADP1 Publication
Nucleotide bindingi63 – 664NADP1 Publication
Nucleotide bindingi93 – 986NADP1 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. response to antibiotic Source: UniProtKB-KW
  5. response to methotrexate Source: UniProtKB-KW
  6. tetrahydrofolate biosynthetic process Source: UniProtKB-UniPathway
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Antibiotic resistance, Methotrexate resistance, One-carbon metabolism, Trimethoprim resistance

Keywords - Ligandi

NADP

Enzyme and pathway databases

BRENDAi1.5.1.3. 3352.
UniPathwayiUPA00077; UER00158.

Names & Taxonomyi

Protein namesi
Recommended name:
Dihydrofolate reductase type 1 from Tn4003 (EC:1.5.1.3)
Gene namesi
Name:dfrA
Encoded oniPlasmid pSK10 Publication
OrganismiStaphylococcus aureus
Taxonomic identifieri1280 [NCBI]
Taxonomic lineageiBacteriaFirmicutesBacilliBacillalesStaphylococcus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi44 – 441A → G: Increases trimethoprim sensitivity; when associated with F-99. 1 Publication
Mutagenesisi99 – 991Y → F: Increases trimethoprim sensitivity; when associated with G-44. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 161160Dihydrofolate reductase type 1 from Tn4003PRO_0000186405Add
BLAST

Proteomic databases

PRIDEiP13955.

Structurei

Secondary structure

1
161
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi3 – 108Combined sources
Beta strandi14 – 174Combined sources
Helixi26 – 3611Combined sources
Beta strandi39 – 446Combined sources
Helixi45 – 517Combined sources
Beta strandi58 – 636Combined sources
Beta strandi75 – 773Combined sources
Helixi81 – 844Combined sources
Beta strandi90 – 945Combined sources
Helixi96 – 1027Combined sources
Turni103 – 1053Combined sources
Beta strandi107 – 11610Combined sources
Beta strandi120 – 1234Combined sources
Turni129 – 1313Combined sources
Beta strandi132 – 1398Combined sources
Beta strandi143 – 1453Combined sources
Beta strandi150 – 1578Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2W9SX-ray1.80A/B/C/D/E/F1-161[»]
2W9TX-ray2.35A/B1-161[»]
ProteinModelPortaliP13955.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP13955.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini2 – 157156DHFRPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni6 – 83Substrate binding

Sequence similaritiesi

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

Phylogenomic databases

KOiK00287.

Family and domain databases

Gene3Di3.40.430.10. 1 hit.
InterProiIPR012259. DHFR.
IPR024072. DHFR-like_dom.
IPR017925. DHFR_CS.
IPR001796. DHFR_dom.
[Graphical view]
PfamiPF00186. DHFR_1. 1 hit.
[Graphical view]
PIRSFiPIRSF000194. DHFR. 1 hit.
PRINTSiPR00070. DHFR.
SUPFAMiSSF53597. SSF53597. 1 hit.
PROSITEiPS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P13955-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTLSIIVAHD KQRVIGYQNQ LPWHLPNDLK HIKQLTTGNT LVMARKTFNS
60 70 80 90 100
IGKPLPNRRN VVLTNQASFH HEGVDVINSL DEIKELSGHV FIFGGQTLYE
110 120 130 140 150
AMIDQVDDMY ITVIDGKFQG DTFFPPYTFE NWEVESSVEG QLDEKNTIPH
160
TFLHLVRRKG K
Length:161
Mass (Da):18,461
Last modified:January 23, 2007 - v3
Checksum:iF829D6109A3AF3A0
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X13290 Genomic DNA. Translation: CAA31649.1.
Y07536 Genomic DNA. Translation: CAA68824.1.
PIRiS04164.
RefSeqiNP_877983.1. NC_005054.1.
YP_002790943.1. NC_012547.1.
YP_003813115.1. NC_014369.1.
YP_006937652.1. NC_013320.1.
YP_006937707.1. NC_013321.1.
YP_006938354.1. NC_013338.1.
YP_006938562.1. NC_013343.1.
YP_009074036.1. NG_034438.1.
YP_009075639.1. NG_035071.1.

Genome annotation databases

GeneIDi13874802.
13874858.
13875495.
13875735.
2598376.
7751508.
9487075.
KEGGipg:13874802.
pg:13874858.
pg:13875495.
pg:13875735.
pg:2598376.
pg:7751508.
pg:9487075.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X13290 Genomic DNA. Translation: CAA31649.1.
Y07536 Genomic DNA. Translation: CAA68824.1.
PIRiS04164.
RefSeqiNP_877983.1. NC_005054.1.
YP_002790943.1. NC_012547.1.
YP_003813115.1. NC_014369.1.
YP_006937652.1. NC_013320.1.
YP_006937707.1. NC_013321.1.
YP_006938354.1. NC_013338.1.
YP_006938562.1. NC_013343.1.
YP_009074036.1. NG_034438.1.
YP_009075639.1. NG_035071.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2W9SX-ray1.80A/B/C/D/E/F1-161[»]
2W9TX-ray2.35A/B1-161[»]
ProteinModelPortaliP13955.
ModBaseiSearch...
MobiDBiSearch...

Proteomic databases

PRIDEiP13955.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi13874802.
13874858.
13875495.
13875735.
2598376.
7751508.
9487075.
KEGGipg:13874802.
pg:13874858.
pg:13875495.
pg:13875735.
pg:2598376.
pg:7751508.
pg:9487075.

Phylogenomic databases

KOiK00287.

Enzyme and pathway databases

UniPathwayiUPA00077; UER00158.
BRENDAi1.5.1.3. 3352.

Miscellaneous databases

EvolutionaryTraceiP13955.

Family and domain databases

Gene3Di3.40.430.10. 1 hit.
InterProiIPR012259. DHFR.
IPR024072. DHFR-like_dom.
IPR017925. DHFR_CS.
IPR001796. DHFR_dom.
[Graphical view]
PfamiPF00186. DHFR_1. 1 hit.
[Graphical view]
PIRSFiPIRSF000194. DHFR. 1 hit.
PRINTSiPR00070. DHFR.
SUPFAMiSSF53597. SSF53597. 1 hit.
PROSITEiPS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Trimethoprim resistance transposon Tn4003 from Staphylococcus aureus encodes genes for a dihydrofolate reductase and thymidylate synthetase flanked by three copies of IS257."
    Rouch D.A., Messeroti L.J., Loo L.S.L., Jackson C.A., Skurray R.A.
    Mol. Microbiol. 3:161-175(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Transposon: Tn4003.
  2. "Identical genes for trimethoprim-resistant dihydrofolate reductase from Staphylococcus aureus in Australia and central Europe."
    Burdeska A., Ott M., Bannwarth W., Then R.L.
    FEBS Lett. 266:159-162(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: 157/4696.
  3. "Structural comparison of chromosomal and exogenous dihydrofolate reductase from Staphylococcus aureus in complex with the potent inhibitor trimethoprim."
    Heaslet H., Harris M., Fahnoe K., Sarver R., Putz H., Chang J., Subramanyam C., Barreiro G., Miller J.R.
    Proteins 76:706-717(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH NADPH AND TRIMETHOPRIM, MUTAGENESIS OF ALA-44 AND TYR-99.

Entry informationi

Entry nameiDYRA_STAAU
AccessioniPrimary (citable) accession number: P13955
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 23, 2007
Last modified: April 1, 2015
This is version 93 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

There are two DhfR isozymes in S.aureus, this one is plasmid-encoded and is resistant to trimethoprim.

Keywords - Technical termi

3D-structure, Plasmid

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.