Reviewed, UniProtKB/Swiss-Prot P00383 (DYR21_ECOLX)

Names and origin

Protein names	Recommended name:     Dihydrofolate reductase type 2     EC=1.5.1.3 Alternative name(s):     Dihydrofolate reductase type II
Encoded on	Plasmid R67
Organism	Escherichia coli
Taxonomic identifier	562 [NCBI]
Taxonomic lineage	Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacteriales › Enterobacteriaceae › Escherichia

Protein attributes

Sequence length	78 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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	Type II plasmid-specified enzyme is practically insensitive to trimethoprim and methotrexate. 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.

Ontologies

Keywords
Biological process	Antibiotic resistance Methotrexate resistance One-carbon metabolism Trimethoprim resistance
Ligand	NADP
Molecular function	Oxidoreductase
Technical term	3D-structure Direct protein sequencing Plasmid
Gene Ontology (GO)
Biological process	one-carbon compound metabolic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW photosynthesis Inferred from electronic annotation. Source: InterPro response to antibiotic Inferred from electronic annotation. Source: UniProtKB-KW response to drug Inferred from electronic annotation. Source: InterPro response to methotrexate Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	plastid Inferred from electronic annotation. Source: InterPro
Molecular function	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 – 78

78

Dihydrofolate reductase type 2

PRO_0000186435

Secondary structure

1

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78

Helix Strand Turn

Details...

Beta strand

29 – 36

8

Beta strand

39 – 46

8

Beta strand

52 – 62

11

Beta strand

66 – 70

5

Helix

71 – 73

3

Beta strand

74 – 76

3

Sequences

	Sequence		Length	Mass (Da)
	P00383-1 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 0BDB0B9146529417	FASTA	78	8,446
	10 20 30 40 50 60 MERSSNEVSN PVAGNFVFPS NATFGMGDRV RKKSGAAWQG QIVGWYCTNL TPEGYAVESE 70 AHPGSVQIYP VAALERIN

References

[1]	"Nucleotide sequence of the dihydrofolate-reductase gene borne by the plasmid R67 and conferring methotrexate resistance." Brisson N., Hohn T. Gene 28:271-275(1984) [PubMed: 6735180] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"The amino acid sequence of the trimethoprim-resistant dihydrofolate reductase specified in Escherichia coli by R-plasmid R67." Stone D., Smith S.L. J. Biol. Chem. 254:10857-10861(1979) [PubMed: 387758] [Abstract] Cited for: PROTEIN SEQUENCE.
[3]	"A plasmid-encoded dihydrofolate reductase from trimethoprim-resistant bacteria has a novel D2-symmetric active site." Narayana N., Matthews D.A., Howell E.E., Nguyen-Huu X. Nat. Struct. Biol. 2:1018-1025(1995) [PubMed: 7583655] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 17-78.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

K02118 Genomic DNA. Translation: AAA26083.1.

PIR

RDECD6. A91512.

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1VIE	X-ray	1.70	A	17-78	[»]
1VIF	X-ray	1.80	A	17-78	[»]
2GQV	X-ray	1.10	A	17-78	[»]
2P4T	X-ray	1.15	A	17-78	[»]
2RH2	X-ray	0.96	A	17-78	[»]
2RK1	X-ray	1.26	A	17-78	[»]
2RK2	X-ray	1.90	A	17-78	[»]

ModBase

Search...

Enzyme and pathway databases

BRENDA

1.5.1.3. 246.

Family and domain databases

InterPro

IPR009159. Dhfr_type_II.
[Graphical view]

Pfam

PF06442. DHFR_2. 1 hit.
[Graphical view]

PIRSF

PIRSF000199. Dhfr_type_II. 1 hit.

ProtoNet

Search...

Entry information

Entry name

DYR21_ECOLX

Accession

Primary (citable) accession number: P00383

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	June 16, 2009
This is version 63 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)