Reviewed, UniProtKB/Swiss-Prot P00382 (DYR1_ECOLX)

Names and origin

Protein names

Recommended name:
    Dihydrofolate reductase type 1
    EC=1.5.1.3
Alternative name(s):
    Dihydrofolate reductase type I
    Trimethoprim resistance protein

Gene names

Name:

dhfrI

Encoded on

Plasmid IncI1 R483 Ref.2 Ref.4
Plasmid pLMO150 Ref.3
Plasmid pLMO229 Ref.3

Organism

Escherichia coli

Taxonomic identifier

562 [NCBI]

Taxonomic lineage

Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacteriales › Enterobacteriaceae › Escherichia

Protein attributes

Sequence length	157 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis By similarity.
Catalytic activity	5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH.
Pathway	Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate: step 1/1.
Subunit structure	Homodimer.
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	Direct protein sequencing Plasmid Transposable element
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 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
	Chain	1 – 157	157	Dihydrofolate reductase type 1		PRO_0000186420
Regions
	Domain	2 – 156	155	DHFR
Natural variations
	Natural variant	75	1	L → V in plasmid pLMO229.

Sequences

	Sequence		Length	Mass (Da)
	P00382-1 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 487F818A40E4991B	FASTA	157	17,575
	10 20 30 40 50 60 MKLSLMVAIS KNGVIGNGPD IPWSAKGEQL LFKAITYNQW LLVGRKTFES MGALPNRKYA 70 80 90 100 110 120 VVTRSSFTSD NENVLIFPSI KDALTNLKKI TDHVIVSGGG EIYKSLIDQV DTLHISTIDI 130 140 150 EPEGDVYFPE IPSNFRPVFT QDFASNINYS YQIWQKG

References

[1]	"The nucleotide sequence of the trimethoprim-resistant dihydrofolate reductase gene harbored by Tn7." Fling M.E., Richards C. Nucleic Acids Res. 11:5147-5158(1983) [PubMed: 6308574] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Transposon: Tn7.
[2]	"Expression of the plasmid-encoded type I dihydrofolate reductase gene in cultured mammalian cells: a novel selectable marker." Simonsen C.S., Walter M., Levinson A.D. Nucleic Acids Res. 16:2235-2246(1988) [PubMed: 3357775] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"The dhfrI trimethoprim resistance gene of Tn7 can be found at specific sites in other genetic surroundings." Sundstroem L., Skoeld O. Antimicrob. Agents Chemother. 34:642-650(1990) [PubMed: 2188588] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"R plasmid dihydrofolate reductase with a dimeric subunit structure." Novak P., Stone D., Burchall J.J. J. Biol. Chem. 258:10956-10959(1983) [PubMed: 6350298] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-34.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X00926 Genomic DNA. Translation: CAA25445.1. X17477 Genomic DNA. Translation: CAA35509.1. X17478 Genomic DNA. Translation: CAA35512.1.
PIR	RDECD7. S03651.
RefSeq	NP_065309.1. YP_190212.1.
3D structure databases
ModBase	Search...
Genome annotation databases
GeneID	1238688. 3244885.
Enzyme and pathway databases
BRENDA	1.5.1.3. 246.
Family and domain databases
InterPro	IPR012259. DHFR. IPR017925. Dihydrofolate_reductase_CS. IPR001796. Dihydrofolate_reductase_dom. [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

DYR1_ECOLX

Accession

Primary (citable) accession number: P00382
Secondary accession number(s): P13923

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	February 9, 2010
This is version 66 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

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