[1]	NUCLEOTIDE SEQUENCE [MRNA]. PubMed=3339001 [NCBI, ExPASy, EBI, Israel, Japan] Melera P.W., Davide J.P., Oen H.; "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."; J. Biol. Chem. 263:1978-1990(1988).
[2]	NUCLEOTIDE SEQUENCE [MRNA]. TISSUE=Lung fibroblast; PubMed=6366511 [NCBI, ExPASy, EBI, Israel, Japan] Melera P.W., Davide J.P., Hession C.A., Scotto K.W.; "Phenotypic expression in Escherichia coli and nucleotide sequence of two Chinese hamster lung cell cDNAs encoding different dihydrofolate reductases."; Mol. Cell. Biol. 4:38-48(1984).
[3]	ERRATUM. Melera P.W., Davide J.P., Hession C.A., Scotto K.W.; Mol. Cell. Biol. 4:1001-1001(1984).

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.
MISCELLANEOUS: Cell line DC-3F/A3 produces 90% of its dihydrofolate reductase in the 21k pI 6.5 form.
MISCELLANEOUS: Cell line DC-3F/MQ19 produces 90% of its dihydrofolate reductase in the 20k pI 6.7 form (DHFR97).
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.
SIMILARITY: Belongs to the dihydrofolate reductase family.
SIMILARITY: Contains 1 DHFR (dihydrofolate reductase) domain.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

K01164; AAA36974.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
K01165; AAA36976.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
M19869; AAA36970.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

PIR

S42445; S42445.

3D structure databases

HSSP

P00374; 1KMS. [HSSP ENTRY / PDB]

SMR

P04753; 2-186.

ModBase

P04753.

Ontologies

GO:0004146;	Molecular function: dihydrofolate reductase activity (inferred from electronic annotation from InterPro).
GO:0006545;	Biological process: glycine biosynthetic process (inferred from electronic annotation from InterPro).
GO:0009165;	Biological process: nucleotide biosynthetic process (inferred from electronic annotation from InterPro).
GO:0006730;	Biological process: one-carbon compound metabolic process (inferred from electronic annotation from UniProtKB-KW).
GO:0055114;	Biological process: oxidation reduction (inferred from electronic annotation from UniProtKB-KW).
GO:0031427;	Biological process: response to methotrexate (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.

Family and domain databases

InterPro

IPR001796; DHFR_reg.
Graphical view of domain structure.

Pfam

PF00186; DHFR_1; 1.
Pfam graphical view of domain structure.

PRINTS

PR00070; DHFR.

PROSITE

PS00075; DHFR_1; 1.
PS51330; DHFR_2; 1.
PROSITE graphical view of domain structure (profiles).

ProtoNet

P04753.

Phylogenomic databases

HOVERGEN

P04753; -.

Other

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Methotrexate resistance; NADP; One-carbon metabolism; Oxidoreductase; Polymorphism.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`INIT_MET`	`1 1`		`Removed.`
`CHAIN`	`2 187`	`186`	`Dihydrofolate reductase.`	`PRO_0000186363`
`DOMAIN`	`4 185`	`182`	`DHFR.`
`REGION`	`8 37`	`30`	`Involved in methotrexate binding (Potential).`
`REGION`	`60 70`	`11`	`Involved in methotrexate binding (Potential).`
`BINDING`	`137 137`		`Methotrexate (Potential).`
`VARIANT`	`23 23`	`1`	`F -> L (in MQ19-97).`
`VARIANT`	`96 96`	`1`	`D -> N (in MQ19-97).`

Sequence information

Length: 187 AA [This is the length of the unprocessed precursor]

Molecular weight: 21660 Da [This is the MW of the unprocessed precursor]

CRC64: A91F85A74658C6F3 [This is a checksum on the sequence]

        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

P04753 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools