Reviewed, UniProtKB/Swiss-Prot Q920D2 (DYR_RAT)

Names and origin

Protein names

Recommended name:
    Dihydrofolate reductase
    EC=1.5.1.3

Gene names

Name:

Dhfr

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

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

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 transcript 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 By similarity.
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
Gene Ontology (GO)
Biological process	dihydrofolate metabolic process Ref.1 Inferred from direct assay. Source: RGD 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 nicotine Inferred from expression pattern. Source: RGD tetrahydrofolate biosynthetic process Ref.1 Inferred from direct assay. Source: RGD
Cellular component	soluble fraction Inferred from direct assay. Source: RGD
Molecular function	NADP or NADPH binding Inferred from direct assay. Source: RGD dihydrofolate reductase activity Ref.1 Inferred from sequence or structural similarity. Source: UniProtKB dihydrofolic acid binding Inferred from direct assay. Source: RGD 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
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 187	186	Dihydrofolate reductase		PRO_0000186366
Regions
	Domain	4 – 185	182	DHFR
	Nucleotide binding	16 – 22	7	NADP By similarity
	Nucleotide binding	55 – 57	3	NADP By similarity
	Nucleotide binding	77 – 79	3	NADP By similarity
	Nucleotide binding	117 – 124	8	NADP By similarity
	Region	31 – 36	6	Substrate binding By similarity
Sites
	Binding site	10	1	NADP; via amide nitrogen and carbonyl oxygen By similarity
	Binding site	71	1	Substrate By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q920D2-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: FE1DB4F3515F8B26	FASTA	187	21,638
	10 20 30 40 50 60 MVRPLNCIVA VSQNMGIGKN GDLPWPLLRN EFKYFQRMTT TSSVEGKQNL VIMGRKTWFS 70 80 90 100 110 120 IPEKNRPLKD RINIVLSREL KEPPQGAHFL AKSLDDALKL IEQPELASKV DMVWVVGGSS 130 140 150 160 170 180 VYQEAMNQPG HLRLFVTRIM QEFESDTFFP EIDLEKYKLL PEYPGVLSEI QEEKGIKYKF EVYEKKD

References

[1]	"Isolation of rat dihydrofolate reductase gene and characterization of recombinant enzyme." Wang Y., Bruenn J.A., Queener S.F., Cody V. Antimicrob. Agents Chemother. 45:2517-2523(2001) [PubMed: 11502523] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF318150 mRNA. Translation: AAL11500.1.
IPI	IPI00200419.
RefSeq	NP_569084.1.
UniGene	Rn.24681
3D structure databases
SMR	Q920D2. Positions 2-187.
ModBase	Search...
Protein-protein interaction databases
STRING	Q920D2.
PTM databases
PhosphoSite	Q920D2.
Proteomic databases
PRIDE	Q920D2.
Genome annotation databases
Ensembl	ENSRNOT00000018259; ENSRNOP00000018259; ENSRNOG00000013521; Rattus norvegicus. [Genome view]
GeneID	24312.
KEGG	rno:24312.
NMPDR	fig|10116.3.peg.15341.
UCSC	NM_130400. rat.
Organism-specific databases
CTD	24312.
RGD	2500. Dhfr.
Phylogenomic databases
eggNOG	maNOG18401.
HOVERGEN	Q920D2.
InParanoid	Q920D2.
OMA	PLNCIVA.
OrthoDB	EOG97M4J0.
PhylomeDB	Q920D2.
Enzyme and pathway databases
BRENDA	1.5.1.3. 248.
Gene expression databases
ArrayExpress	Q920D2.
Genevestigator	Q920D2.
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...
Other Resources
BindingDB	Q920D2.
NextBio	602953.

Entry information

Entry name

DYR_RAT

Accession

Primary (citable) accession number: Q920D2

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 20, 2005
Last sequence update:	January 23, 2007
Last modified:	February 9, 2010
This is version 58 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)