Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

DHFR (P00374) - Overview - Molecular Target Synopsis

Protein


DHFR, Dihydrofolate reductase
Enzyme Classification 1.5.1.3
UniProt P00374

Also Known as DYR_HUMAN, DHFR

Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFR2. Homodimer.

6A7E
HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH NADPH AND BT2
RCSB/PDB
Inspect Structure
See all 3D Structures for DHFR

Isoforms / Transcripts (Protein Coding)


Drugs


DHFR is targeted by Approved Drugs Raltitrexed, Pralatrexate, Pemetrexed, Methotrexate, Pemetrexed. (see details)
Raltitrexed
Pralatrexate
Pemetrexed
Methotrexate
Pemetrexed

Sub-cellular localization


UniProt: DHFR is active in the following subcellular-locations: cytoplasm, mitochondrion.
GO terms: DHFR is active in the following subcellular-locations: cytosol, mitochondrion.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project DHFR has gain in 2 cell-lines, loss in 1 cell-lines and no signal in 1002 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: RPMI_8226, CCRF_CEM, COLO205

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: TK, COLO 206F, SK-N-DZ

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: HeLa-S3, HSMM, A549

(see details)

3D Structures


For DHFR there are:
79 structures (93 chains) solved
78 are solved in complex with at least one small molecule ligand
13 are solved with an approved drug

DHFR is solved in complex with the approved drug(s):

FOL/FOLIC ACID (1DHF_A, 1DHF_B, 1DRF_A, 2W3B_A, 2W3B_B, 2W3M_A, 2W3M_B, 4KEB_B, 4KFJ_B, 4M6K_A),
TOP/TRIMETHOPRIM (2W3A_A, 2W3A_B, 3N0H_A, 3S3V_A),
MTX/METHOTREXATE (1DLS_A, 1U72_A, 3EIG_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


DHFR has been screened with 1594 compounds (2915 bioactivities), 495 compounds have bioactivities that show binding affinity of <= 500nM (786 bioactivities). (see details)