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

DNMT1 (P26358) - Overview - Molecular Target Synopsis

Protein


DNMT1, DNA (cytosine-5)-methyltransferase 1
Enzyme Classification 2.1.1.37
UniProt P26358

Also Known as DNMT1_HUMAN, DNMT1, AIM, CXXC9, DNMT

Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is essential for epigenetic inheritance. Associates with chromatin during G2 and M phases to maintain DNA methylation independently of replication. It is responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Mediates transcriptional repression by direct binding to HDAC2. In association with DNMT3B and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Also required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). Promotes tumor growth (PubMed:24623306). Homodimer (PubMed:19173286). Forms a stable complex with E2F1, BB1 and HDAC1 (PubMed:10888886). Forms a complex with DMAP1 and HDAC2, with direct interaction (PubMed:10888872). Interacts with the PRC2/EED-EZH2 complex (PubMed:16357870). Probably part of a corepressor complex containing ZNF304, TRIM28, SETDB1 and DNMT1 (PubMed:24623306). Interacts with UHRF1; promoting its recruitment to hemimethylated DNA (PubMed:21745816). Interacts with USP7, promoting its deubiquitination (PubMed:21745816). Interacts with PCNA (PubMed:9302295). Interacts with MBD2 and MBD3 (PubMed:10947852). Interacts with DNMT3A and DNMT3B (PubMed:12145218). Interacts with UBC9 (PubMed:19450230). Interacts with CSNK1D (By similarity). Interacts with HDAC1 (By similarity). Interacts with BAZ2A/TIP5.

5YDR
STRUCTURE OF DNMT1 RFTS DOMAIN IN COMPLEX WITH UBIQUITIN
RCSB/PDB
Inspect Structure
See all 3D Structures for DNMT1

Isoforms / Transcripts (Protein Coding)


Drugs


DNMT1 is targeted by Approved Drugs Azacitidine, Decitabine. (see details)
Azacitidine
Decitabine

Sub-cellular localization


UniProt: DNMT1 is active in the following subcellular-locations: nucleus.
GO terms: DNMT1 is active in the following subcellular-locations: nucleoplasm, nucleus, pericentric heterochromatin, replication fork.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project DNMT1 has gain in 1 cell-lines, loss in 0 cell-lines and no signal in 1004 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SNB_75, MDA_N, MDA_MB_435

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: OCI-M2, MOLM-16, SU-DHL-5

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: SK-N-SH, K562, HeLa-S3

(see details)

3D Structures


For DNMT1 there are:
9 structures (11 chains) solved
4 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

DNMT1 is solved in complex with the approved drug(s):

BGC/DEXTROSE (3EPZ_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


DNMT1 has been screened with 313 compounds (408 bioactivities), 4 compounds have bioactivities that show binding affinity of <= 500nM (4 bioactivities). (see details)