Reviewed, UniProtKB/Swiss-Prot P00375 (DYR_MOUSE)

Names and origin

Protein names

Recommended name:
    Dihydrofolate reductase
    EC=1.5.1.3

Gene names

Name:

Dhfr

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	187 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	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	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 compound metabolic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	NADP or NADPH binding Inferred from electronic annotation. Source: InterPro dihydrofolate reductase activity Inferred from direct assay. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.5

Chain

2 – 187

186

Dihydrofolate reductase

PRO_0000186364

Regions

Domain

4 – 185

182

DHFR

Natural variations

Natural variant

23

1

L → R in a form with an abnormally low affinity for methotrexate.

Natural variant

32

1

F → W in L5178Y cell line; methotrexate-resistant.

Experimental info

Sequence conflict

4

1

P → A Ref.6

Sequence conflict

14

1

N → D in CAA39544. Ref.3

Sequence conflict

123

1

Q → E AA sequence Ref.5

Sequence conflict

123

1

Q → E in AAA37525. Ref.8

Sequence conflict

124

1

E → Q AA sequence Ref.5

Sequence conflict

128

1

Q → E AA sequence Ref.5

Sequence conflict

174

1

K → D AA sequence Ref.5

Secondary structure

1

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187

Helix Strand Turn

Details...

Beta strand

4 – 12

9

Helix

29 – 40

12

Beta strand

48 – 54

7

Helix

55 – 60

6

Helix

63 – 65

3

Beta strand

71 – 76

6

Beta strand

88 – 93

6

Helix

94 – 101

8

Helix

104 – 107

4

Beta strand

110 – 117

8

Helix

119 – 126

8

Beta strand

127 – 130

4

Beta strand

132 – 139

8

Beta strand

146 – 148

3

Turn

154 – 156

3

Beta strand

157 – 159

3

Beta strand

171 – 173

3

Beta strand

176 – 185

10

Sequences

	Sequence		Length	Mass (Da)
	P00375-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 47AEF15F879B119C	FASTA	187	21,606
	10 20 30 40 50 60 MVRPLNCIVA VSQNMGIGKN GDLPWPPLRN EFKYFQRMTT TSSVEGKQNL VIMGRKTWFS 70 80 90 100 110 120 IPEKNRPLKD RINIVLSREL KEPPRGAHFL AKSLDDALRL IEQPELASKV DMVWIVGGSS 130 140 150 160 170 180 VYQEAMNQPG HLRLFVTRIM QEFESDTFFP EIDLGKYKLL PEYPGVLSEV QEEKGIKYKF EVYEKKD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure of amplified normal and variant dihydrofolate reductase genes in mouse sarcoma S180 cells." Crouse G.F., Simonsen C.C., McEwan R.N., Schimke R.T. J. Biol. Chem. 257:7887-7897(1982) [PubMed: 6282858] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Isolation and expression of an altered mouse dihydrofolate reductase cDNA." Simonsen C.C., Levinson A.D. Proc. Natl. Acad. Sci. U.S.A. 80:2495-2499(1983) [PubMed: 6573667] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Isolation and characterization of a variant dihydrofolate reductase cDNA from methotrexate-resistant murine L5178Y cells." McIvor R.S., Simonsen C.C. Nucleic Acids Res. 18:7025-7032(1990) [PubMed: 2263462] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N. Tissue: Mammary gland.
[5]	"The amino acid sequence of dihydrofolate reductase from the mouse lymphoma L1210." Stone D., Paterson S.J., Raper J.H., Phillips A.W. J. Biol. Chem. 254:480-488(1979) [PubMed: 762074] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-187. Tissue: Lymphoma.
[6]	"Heterogeneity at the 5' termini of mouse dihydrofolate reductase mRNAs. Evidence for multiple promoter regions." McGrogan M., Simonsen C.C., Smouse D.T., Farnham P.J., Schimke R.T. J. Biol. Chem. 260:2307-2314(1985) [PubMed: 2982814] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-28.
[7]	"Structure and genomic organization of the mouse dihydrofolate reductase gene." Nunberg J.H., Kaufman R.J., Chang A.C.Y., Cohen S.N., Schimke R.T. Cell 19:355-364(1980) [PubMed: 6244105] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-24; 50-127 AND 154-187.
[8]	"Phenotypic expression in E. coli of a DNA sequence coding for mouse dihydrofolate reductase." Chang A.C.Y., Nunberg J.H., Kaufman R.J., Erlich H.A., Schimke R.T., Cohen S.N. Nature 275:617-624(1978) [PubMed: 360074] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-24 AND 50-127.
[9]	"Nucleotide sequence surrounding multiple polyadenylation sites in the mouse dihydrofolate reductase gene." Setzer D.R., McGrogan M., Schimke R.T. J. Biol. Chem. 257:5143-5147(1982) [PubMed: 6121807] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 163-187.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

V00734 mRNA. Translation: CAA24112.1.
X56066 mRNA. Translation: CAA39544.1.
BC005796 mRNA. Translation: AAH05796.1.
M10071 Genomic DNA. Translation: AAA37637.1.
L26316 mRNA. Translation: AAA37523.1.
J00387 , J00382, J00383, J00384, J00385, J00386 Genomic DNA. Translation: AAA37638.1.
V00731 mRNA. Translation: CAB43539.2.
M10722 mRNA. Translation: AAA37524.1.
M10811 mRNA. Translation: AAA37525.1.
V00733 Genomic DNA. Translation: CAA24111.1.

IPI

IPI00230042.

PIR

RDMSD. S13096.

RefSeq

NP_034179.1.

UniGene

Mm.23695

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1U70	X-ray	2.50	A	2-186	[»]
2FZJ	X-ray	2.00	A	2-186	[»]
3D80	X-ray	1.40	A	2-187	[»]
3D84	X-ray	1.90	X	2-187	[»]

ModBase

Search...

PTM databases

PhosphoSite

P00375.

Proteomic databases

PRIDE

P00375.

Genome annotation databases

Ensembl

ENSMUSG00000021707. Mus musculus. [Contig view]

GeneID

13361.

KEGG

mmu:13361.

Organism-specific databases

MGI

MGI:94890. Dhfr.

Phylogenomic databases

HOGENOM

P00375.

HOVERGEN

P00375.

OMA

P00375. PLNCIVA.

Enzyme and pathway databases

BRENDA

1.5.1.3. 244.

Gene expression databases

ArrayExpress

P00375.

Bgee

P00375.

CleanEx

MM_DHFR.

GermOnline

ENSMUSG00000021707. Mus musculus.

Family and domain databases

InterPro

IPR012259. DHFR.
IPR001796. DHFR_reg.
IPR017925. Dihydrofolate_reductase_CS.
[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...

Other Resources

NextBio

283696.

SOURCE

Search...

Entry information

Entry name

DYR_MOUSE

Accession

Primary (citable) accession number: P00375
Secondary accession number(s): P70693 , Q61485, Q61487, Q61579

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 93 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)