Protein Description

Gene Symbol DHFR
Entrez ID 1719
Uniprot ID P00374
Description dihydrofolate reductase
Chromosomal Location chr5: 80,626,228-80,654,983
Ontology GO ID GO Term Definition Evidence

BP

GO:0000082

G1/S transition of mitotic cell cycle

The mitotic cell cycle transition by which a cell in G1 commits to S phase. The process begins with the build up of G1 cyclin-dependent kinase (G1 CDK), resulting in the activation of transcription of G1 cyclins. The process ends with the positive feedback of the G1 cyclins on the G1 CDK which commits the cell to S phase, in which DNA replication is initiated.

TAS

BP

GO:0000083

regulation of transcription involved in G1/S transition of mitotic cell cycle

Any process that regulates transcription such that the target genes are involved in the transition between G1 and S phase of the mitotic cell cycle.

TAS

BP

GO:0006545

glycine biosynthetic process

The chemical reactions and pathways resulting in the formation of glycine, aminoethanoic acid.

IEA

BP

GO:0006729

tetrahydrobiopterin biosynthetic process

The chemical reactions and pathways resulting in the formation of tetrahydrobiopterin, the reduced form of biopterin (2-amino-4-hydroxy-6-(1,2-dihydroxypropyl)-pteridine). It functions as a hydroxylation coenzyme, e.g. in the conversion of phenylalanine to tyrosine.

IMP|ISS

BP

GO:0006730

one-carbon metabolic process

The chemical reactions and pathways involving the transfer of one-carbon units in various oxidation states.

IEA

BP

GO:0009165

nucleotide biosynthetic process

The chemical reactions and pathways resulting in the formation of nucleotides, any nucleoside that is esterified with (ortho)phosphate or an oligophosphate at any hydroxyl group on the glycose moiety; may be mono-, di- or triphosphate; this definition includes cyclic-nucleotides (nucleoside cyclic phosphates).

IEA

BP

GO:0031103

axon regeneration

The regrowth of axons following their loss or damage.

ISS

BP

GO:0031427

response to methotrexate

Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a methotrexate stimulus. Methotrexate is 4-amino-10-methylformic acid, a folic acid analogue that is a potent competitive inhibitor of dihydrofolate reductase.

ISS

BP

GO:0046452

dihydrofolate metabolic process

The chemical reactions and pathways involving dihydrofolate, the dihydroxylated derivative of folate.

IDA

BP

GO:0046653

tetrahydrofolate metabolic process

The chemical reactions and pathways involving tetrahydrofolate, 5,6,7,8-tetrahydrofolic acid, a folate derivative bearing additional hydrogens on the pterin group.

IDA

BP

GO:0046654

tetrahydrofolate biosynthetic process

The chemical reactions and pathways resulting in the formation of tetrahydrofolate, 5,6,7,8-tetrahydrofolic acid, a folate derivative bearing additional hydrogens on the pterin group.

IDA|IEA

BP

GO:0046655

folic acid metabolic process

The chemical reactions and pathways involving folic acid, pteroylglutamic acid. Folic acid is widely distributed as a member of the vitamin B complex and is essential for the synthesis of purine and pyrimidines.

ISS|TAS

BP

GO:0051000

positive regulation of nitric-oxide synthase activity

Any process that activates or increases the activity of the enzyme nitric-oxide synthase.

ISS

BP

GO:0055114

oxidation-reduction process

A metabolic process that results in the removal or addition of one or more electrons to or from a substance, with or without the concomitant removal or addition of a proton or protons.

IDA

BP

GO:2000121

regulation of removal of superoxide radicals

Any process that modulates the frequency, rate or extent of removal of superoxide radicals.

ISS

CC

GO:0005575

cellular_component

The part of a cell or its extracellular environment in which a gene product is located. A gene product may be located in one or more parts of a cell and its location may be as specific as a particular macromolecular complex, that is, a stable, persistent association of macromolecules that function together.

ND

CC

GO:0005654

nucleoplasm

That part of the nuclear content other than the chromosomes or the nucleolus.

TAS

CC

GO:0005829

cytosol

The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.

TAS

MF

GO:0003729

mRNA binding

Interacting selectively and non-covalently with messenger RNA (mRNA), an intermediate molecule between DNA and protein. mRNA includes UTR and coding sequences, but does not contain introns.

IDA

MF

GO:0004146

dihydrofolate reductase activity

Catalysis of the reaction: 5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+.

IDA|ISS|NAS

MF

GO:0005542

folic acid binding

Interacting selectively and non-covalently with folic acid, pteroylglutamic acid. Folic acid is widely distributed as a member of the vitamin B complex and is essential for the synthesis of purine and pyrimidines.

IDA

MF

GO:0008144

drug binding

Interacting selectively and non-covalently with a drug, any naturally occurring or synthetic substance, other than a nutrient, that, when administered or applied to an organism, affects the structure or functioning of the organism; in particular, any such substance used in the diagnosis, prevention, or treatment of disease.

IDA

MF

GO:0033560

folate reductase activity

Catalysis of the reaction: 7,8-dihydrofolate + NADP+ = folate + NADPH + H+.

TAS

MF

GO:0051870

methotrexate binding

Interacting selectively and non-covalently with methotrexate, an antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of tetrahydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.

IDA

MF

GO:0070402

NADPH binding

Interacting selectively and non-covalently with the reduced form, NADPH, of nicotinamide-adenine dinucleotide phosphate, a coenzyme involved in many redox and biosynthetic reactions.

IDA

Domain ID Description

IPR001796

Dihydrofolate reductase domain

IPR012259

Dihydrofolate reductase

IPR017925

Dihydrofolate reductase conserved site

IPR024072

Dihydrofolate reductase-like domain

Pathway ID Pathway Term Pathway Source

hsa00670

One carbon pool by folate

KEGG

hsa00790

Folate biosynthesis

KEGG

hsa01100

Metabolic pathways

KEGG

hsa01523

Antifolate resistance

KEGG

WP241

One Carbon Metabolism

WikiPathways

WP1601

Fluoropyrimidine Activity

WikiPathways

WP176

Folate Metabolism

WikiPathways

WP404

Nucleotide Metabolism

WikiPathways

WP2446

Retinoblastoma (RB) in Cancer

WikiPathways

WP2525

Trans-sulfuration and one carbon metabolism

WikiPathways

h_g1Pathway

Cell Cycle: G1/S Check Point

BioCarta

UMLS CUI UMLS Term

C0000786

Spontaneous Abortion

C0002888

Anemia, Megaloblastic

C0003873

Rheumatoid Arthritis

C0004352

Autistic Disorder

C0009404

Colorectal Neoplasms

C0016412

Folic Acid Deficiency

C0021361

Female Infertility

C0025521

Inborn Errors Of Metabolism

C0027627

Neoplasm Metastasis

C0027765

Nervous System Disorder

C0029463

Osteosarcoma

C0030312

Pancytopenia

C0041755

Adverse Reaction To Drug

C0860207

Drug-Induced Liver Injury

C1458155

Mammary Neoplasms

Tissue Cell Type

duodenum

glandular cells

epididymis

glandular cells

fallopian tube

glandular cells

lung

macrophages

nasopharynx

respiratory epithelial cells

pancreas

exocrine glandular cells

placenta

decidual cells

placenta

trophoblastic cells

prostate

glandular cells

salivary gland

glandular cells

seminal vesicle

glandular cells

small intestine

glandular cells

stomach

glandular cells

No databases found.

Pubmed ID Author Year Title

22617121

Ouandaogo et al.

2012

Differences in transcriptomic profiles of human cumulus cells isolated from oocytes at GV, MI and MII stages after in vivo andin vitro oocyte maturation

22951915

Haozi et al.

2012

Altered gene expression profile in cumulus cells of mature MII oocytes from patients with polycystic ovary syndrome

Gene Symbol Entrez ID Uniprot ID Score

DHFR

1719

P00374

0.49

ASGR1

432

P07306

0.52

GKAP1

80318

Q5VSY0

0.63

TP53

7157

P04637

0.75

HSPD1

3329

P10809

0.87

AMFR

267

Q9UKV5

0.52

TOMM20

9804

Q15388

0.62

SUMO2

6613

P61956

0.63

UBD

10537

O15205

0.63

FOXL1

2300

Q12952

0.72

FOXB1

27023

Q99853

0.72

THBS1

7057

P07996

0.75

FKBP1A

2280

P62942

0.77

MDM2

4193

Q00987

0.79