Reviewed, UniProtKB/Swiss-Prot P00378 (DYR_CHICK)

Names and origin

Protein names

Recommended name:
    Dihydrofolate reductase
    EC=1.5.1.3

Gene names

Name:

DHFR

Organism

Gallus gallus (Chicken)

Taxonomic identifier

9031 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Archosauria › Dinosauria › Saurischia › Theropoda › Coelurosauria › Aves › Neognathae › Galliformes › Phasianidae › Phasianinae › Gallus

Protein attributes

Sequence length	189 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.
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.
Sequence similarities	Belongs to the dihydrofolate reductase family. Contains 1 DHFR (dihydrofolate reductase) domain.

Ontologies

Keywords
Biological process	Methotrexate resistance One-carbon metabolism
Ligand	NADP
Molecular function	Oxidoreductase
Technical term	3D-structure Direct protein sequencing
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 tetrahydrofolate metabolic process Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	NADP or NADPH binding Inferred from electronic annotation. Source: InterPro dihydrofolate reductase activity Inferred from sequence or structural similarity. Source: UniProtKB drug binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 189

189

Dihydrofolate reductase

PRO_0000186367

Regions

Domain

3 – 184

182

DHFR

Nucleotide binding

15 – 21

7

NADP

Nucleotide binding

54 – 56

3

NADP

Nucleotide binding

76 – 78

3

NADP

Nucleotide binding

116 – 123

8

NADP

Region

30 – 35

6

Substrate binding

Sites

Binding site

9

1

NADP; via amide nitrogen and carbonyl oxygen

Binding site

70

1

Substrate

Experimental info

Sequence conflict

141

1

E → Q AA sequence Ref.2

Secondary structure

1

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189

Helix Strand Turn

Details...

Beta strand

3 – 10

8

Beta strand

15 – 18

4

Helix

28 – 39

12

Beta strand

47 – 53

7

Helix

54 – 59

6

Helix

62 – 64

3

Beta strand

70 – 75

6

Beta strand

87 – 92

6

Helix

93 – 101

9

Helix

103 – 106

4

Beta strand

109 – 114

6

Helix

118 – 126

9

Beta strand

127 – 140

14

Beta strand

145 – 147

3

Turn

153 – 155

3

Beta strand

156 – 158

3

Beta strand

170 – 172

3

Beta strand

175 – 184

10

Sequences

	Sequence		Length	Mass (Da)
	P00378-1 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: BC5F50C94BCA3EDA	FASTA	189	21,650
	10 20 30 40 50 60 VRSLNSIVAV CQNMGIGKDG NLPWPPLRNE YKYFQRMTST SHVEGKQNAV IMGKKTWFSI 70 80 90 100 110 120 PEKNRPLKDR INIVLSRELK EAPKGAHYLS KSLDDALALL DSPELKSKVD MVWIVGGTAV 130 140 150 160 170 180 YKAAMEKPIN HRLFVTRILH EFESDTFFPE IDYKDFKLLT EYPGVPADIQ EEDGIQYKFE VYQKSVLAQ

References

[1]	"Primary structure of chicken liver dihydrofolate reductase." Kumar A.A., Blankenship D.T., Kaufman B.T., Freisheim J.H. Biochemistry 19:667-678(1980) [PubMed: 6766736] [Abstract] Cited for: PROTEIN SEQUENCE.
[2]	"Activation of chicken liver dihydrofolate reductase by urea and guanidine hydrochloride is accompanied by conformational change at the active site." Fan Y.X., Ju M., Zhou J.M., Tsou C.L. Biochem. J. 315:97-102(1996) [PubMed: 8670138] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-22; 138-141 AND 158-161.
[3]	"Crystal structure of chicken liver dihydrofolate reductase complexed with NADP+ and biopterin." McTigue M.A., Davies J.F. II, Kaufman B.T., Kraut J. Biochemistry 31:7264-7273(1992) [PubMed: 1510919] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEXES WITH NADPH AND DIHYDROBIOPTERIN.
+	Additional computationally mapped references.

Cross-references

Sequence databases

IPI

IPI00822128.

PIR

RDCHD. A00390.

UniGene

Gga.2883

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DR1	X-ray	2.20	A	1-189	[»]
1DR2	X-ray	2.30	A	1-189	[»]
1DR3	X-ray	2.30	A	1-189	[»]
1DR4	X-ray	2.40	A	1-189	[»]
1DR5	X-ray	2.40	A	1-189	[»]
1DR6	X-ray	2.40	A	1-189	[»]
1DR7	X-ray	2.40	A	1-189	[»]
8DFR	X-ray	1.70	A	1-189	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

P00378.

Genome annotation databases

Ensembl

ENSGALT00000025122; ENSGALP00000025076; ENSGALG00000015579; Gallus gallus. [Genome view]

Phylogenomic databases

HOVERGEN

P00378.

InParanoid

P00378.

PhylomeDB

P00378.

Enzyme and pathway databases

BRENDA

1.5.1.3. 4.

Family and domain databases

InterPro

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

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

DYR_CHICK

Accession

Primary (citable) accession number: P00378

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	February 9, 2010
This is version 78 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)