Reviewed, UniProtKB/Swiss-Prot P04753 (DYR_MESAU)

Names and origin

Protein names

Recommended name:
    Dihydrofolate reductase
    EC=1.5.1.3

Gene names

Name:

DHFR

Organism

Mesocricetus auratus (Golden hamster)

Taxonomic identifier

10036 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Cricetidae › Cricetinae › Mesocricetus

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)

Catalytic activity	5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH.
Pathway	Cofactor biosynthesis; tetrahydrofolate biosynthesis; tetrahydrofolate from dihydrofolate: step 1/1.
Polymorphism	The sequence shown is that of A3-35. The two clones A3-35 and MQ19-97 represent allelic forms. They differ in their drug sensitivities, possibly because of the difference at position 22.
Miscellaneous	Overexpression of the dihydrofolate gene (generally involving gene amplification) results in resistance to the antitumor antifolate drugs methotrexate (MTX) and methasquin. Cell line DC-3F/A3 produces 90% of its dihydrofolate reductase in the 21k pI 6.5 form. Cell line DC-3F/MQ19 produces 90% of its dihydrofolate reductase in the 20k pI 6.7 form (DHFR97). 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	Methotrexate resistance One-carbon metabolism
Coding sequence diversity	Polymorphism
Ligand	NADP
Molecular function	Oxidoreductase
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 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
	Initiator methionine	1	1	Removed
	Chain	2 – 187	186	Dihydrofolate reductase		PRO_0000186363
Regions
	Domain	4 – 185	182	DHFR
	Region	8 – 37	30	Involved in methotrexate binding Potential
	Region	60 – 70	11	Involved in methotrexate binding Potential
Sites
	Binding site	137	1	Methotrexate Potential
Natural variations
	Natural variant	23	1	F → L in MQ19-97.
	Natural variant	96	1	D → N in MQ19-97.

Sequences

	Sequence		Length	Mass (Da)
	P04753-1 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: A91F85A74658C6F3	FASTA	187	21,660
	10 20 30 40 50 60 MVRPLNCIVA VSQNMGIGKN GDFPWPMLRN EFKYFQRMTT TSSVEGKQNL VIMGRKTWFS 70 80 90 100 110 120 IPEKNRPLKD RINIVLSREL KEPPQGAHFL AKSLDDALKL IEQPELADKV DMVWIVGGSS 130 140 150 160 170 180 VYKEAMNQPG HLRLFVTRIM QEFESDTFFP EIDLEKYKLL PEYPGVLSEV QEEKGIKYKF EVYEKKG

References

[1]	"Antifolate-resistant Chinese hamster cells. Molecular basis for the biochemical and structural heterogeneity among dihydrofolate reductases produced by drug-sensitive and drug-resistant cell lines." Melera P.W., Davide J.P., Oen H. J. Biol. Chem. 263:1978-1990(1988) [PubMed: 3339001] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Phenotypic expression in Escherichia coli and nucleotide sequence of two Chinese hamster lung cell cDNAs encoding different dihydrofolate reductases." Melera P.W., Davide J.P., Hession C.A., Scotto K.W. Mol. Cell. Biol. 4:38-48(1984) [PubMed: 6366511] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lung fibroblast.
[3]	Erratum Melera P.W., Davide J.P., Hession C.A., Scotto K.W. Mol. Cell. Biol. 4:1001-1001(1984)

Cross-references

Sequence databases
EMBLGenBankDDBJ	K01164 mRNA. Translation: AAA36974.1. K01165 mRNA. Translation: AAA36976.1. M19869 mRNA. Translation: AAA36970.1.
PIR	S42445.
3D structure databases
HSSP	HSSP built from PDB template 1KMS based on UniProtKB P00374.
SMR	P04753. Positions 2-186.
ModBase	Search...
Phylogenomic databases
HOVERGEN	P04753.
Enzyme and pathway databases
BRENDA	1.5.1.3. 824.
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...

Entry information

Entry name

DYR_MESAU

Accession

Primary (citable) accession number: P04753

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 60 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)