Reviewed, UniProtKB/Swiss-Prot P13955 (DYRA_STAAU)

Names and origin

Protein names

Recommended name:
    Dihydrofolate reductase type 1 from Tn4003
    EC=1.5.1.3

Gene names

Name:

dfrA

Encoded on

Plasmid pSK1

Organism

Staphylococcus aureus

Taxonomic identifier

1280 [NCBI]

Taxonomic lineage

Bacteria › Firmicutes › Bacillales › Staphylococcus

Protein attributes

Sequence length	161 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Catalytic activity	5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH.
Pathway	Cofactor biosynthesis; tetrahydrofolate biosynthesis; tetrahydrofolate from dihydrofolate: step 1/1.
Miscellaneous	There are two dhfR isozymes in S.aureus, this one is plasmid-encoded and is resistant to trimethoprim. The reaction catalyzed by this enzyme represents an essential step for de novo glycine and purine synthesis, DNA precursor synthesis, and for the conversion of dUMP to dTMP.
Sequence similarities	Belongs to the dihydrofolate reductase family. Contains 1 DHFR (dihydrofolate reductase) domain.

Ontologies

Keywords
Biological process	Antibiotic resistance Methotrexate resistance One-carbon metabolism Trimethoprim resistance
Ligand	NADP
Molecular function	Oxidoreductase
Technical term	3D-structure Plasmid
Gene Ontology (GO)
Biological process	glycine biosynthetic process Inferred from electronic annotation. Source: InterPro nucleotide biosynthetic process Inferred from electronic annotation. Source: InterPro one-carbon compound metabolic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW response to antibiotic Inferred from electronic annotation. Source: UniProtKB-KW response to methotrexate Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	NADP or NADPH binding Inferred from electronic annotation. Source: InterPro dihydrofolate reductase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 161	160	Dihydrofolate reductase type 1 from Tn4003		PRO_0000186405
Regions
	Domain	2 – 157	156	DHFR

Sequences

	Sequence		Length	Mass (Da)
	P13955-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: F829D6109A3AF3A0	FASTA	161	18,461
	10 20 30 40 50 60 MTLSIIVAHD KQRVIGYQNQ LPWHLPNDLK HIKQLTTGNT LVMARKTFNS IGKPLPNRRN 70 80 90 100 110 120 VVLTNQASFH HEGVDVINSL DEIKELSGHV FIFGGQTLYE AMIDQVDDMY ITVIDGKFQG 130 140 150 160 DTFFPPYTFE NWEVESSVEG QLDEKNTIPH TFLHLVRRKG K

References

[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(1989) [PubMed: 2548057] [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(1990) [PubMed: 2365064] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: 157/4696.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

X13290 Genomic DNA. Translation: CAA31649.1.
Y07536 Genomic DNA. Translation: CAA68824.1.

PIR

S04164.

RefSeq

NP_877983.1.
YP_002790943.1.

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2W9S	X-ray	1.80	A/B/C/D/E/F	1-161	[»]
2W9T	X-ray	2.35	A/B	1-161	[»]

ModBase

Search...

Genome annotation databases

GeneID

2598376.
7751508.

Enzyme and pathway databases

BRENDA

1.5.1.3. 95.

Family and domain databases

InterPro

IPR012259. DHFR.
IPR001796. DHFR_reg.
IPR017925. Dihydrofolate_reductase_CS.
[Graphical view]

PANTHER

PTHR11549:SF1. DHFR. 1 hit.

Pfam

PF00186. DHFR_1. 1 hit.
[Graphical view]

PRINTS

PR00070. DHFR.

PROSITE

PS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

DYRA_STAAU

Accession

Primary (citable) accession number: P13955

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 63 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HAMAP (High-quality Automated and Manual Annotation of microbial Proteomes)