DNMT1

The N-terminal part is required for homodimerization and acts as a regulatory domain.

The CXXC-type zinc finger specifically binds to unmethylated CpG dinucleotides, positioning the autoinhibitory linker between the DNA and the active site, thus providing a mechanism to ensure that only hemimethylated CpG dinucleotides undergo methylation.

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).

Neuropathy, hereditary sensory, 1E

HSN1E

A neurodegenerative disorder characterized by adult onset of progressive peripheral sensory loss associated with progressive hearing impairment and early-onset dementia.

None

The disease is caused by variants affecting the gene represented in this entry.

Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant

ADCADN

An autosomal dominant neurologic disorder characterized by adult onset of progressive cerebellar ataxia, narcolepsy, cataplexy, sensorineural deafness, and dementia. More variable features include optic atrophy, sensory neuropathy, psychosis, and depression.

None

The disease is caused by variants affecting the gene represented in this entry.

Sumoylated; sumoylation increases activity.

Acetylation on multiple lysines, mainly by KAT2B/PCAF, regulates cell cycle G(2)/M transition. Deacetylation of Lys-1349 and Lys-1415 by SIRT1 increases methyltransferase activity.

Phosphorylation of Ser-154 by CDKs is important for enzymatic activity and protein stability. Phosphorylation of Ser-143 by AKT1 prevents methylation by SETD7 therebye increasing DNMT1 stability.

Methylation at Lys-142 by SETD7 is necessary for the regulation of DNMT1 proteasomal degradation.

Ubiquitinated by UHRF1; interaction with USP7 counteracts ubiquitination by UHRF1 by promoting deubiquitination and preventing degradation by the proteasome.

Belongs to the class I-like SAM-binding methyltransferase superfamily. C5-methyltransferase family.

Ubiquitous; highly expressed in fetal tissues, heart, kidney, placenta, peripheral blood mononuclear cells, and expressed at lower levels in spleen, lung, brain, small intestine, colon, liver, and skeletal muscle. Isoform 2 is less expressed than isoform 1.

• Nucleus
• Localized to the perinucleolar region.

AIM, CXXC9, DNMT, DNMT1, DNA (cytosine-5)-methyltransferase 1, Dnmt1, CXXC-type zinc finger protein 9, DNA methyltransferase HsaI, MCMT, DNA MTase HsaI, M.HsaI

• entrezGene:1786
• omim:126375
• swissprot:P26358

Proteins

Epigenetics

183165Da