ID:DNMT1_HUMAN DESCRIPTION: RecName: Full=DNA (cytosine-5)-methyltransferase 1; Short=Dnmt1; EC=2.1.1.37; AltName: Full=CXXC-type zinc finger protein 9; AltName: Full=DNA methyltransferase HsaI; Short=DNA MTase HsaI; Short=M.HsaI; AltName: Full=MCMT; FUNCTION: 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. CATALYTIC ACTIVITY: S-adenosyl-L-methionine + DNA = S-adenosyl-L- homocysteine + DNA containing 5-methylcytosine. SUBUNIT: Binds to CSNK1D (By similarity). Homodimer. Interacts with HDAC1 and with PCNA. Forms a complex with DMAP1 and HDAC2, with direct interaction. Forms also a stable complex with E2F1, BB1 and HDAC1. Binds MBD2 and MBD3. Component of complexes containing SUV39H1. Interacts with DNMT3A and DNMT3B. Interacts with the PRC2/EED-EZH2 complex. Interacts with UBC9 and BAZ2A/TIP5. Interacts with UHRF1; promoting its recruitment to hemimethylated DNA. Interacts with USP7, promoting its deubiquitination. INTERACTION: O75530:EED; NbExp=3; IntAct=EBI-719459, EBI-923794; Q15910:EZH2; NbExp=8; IntAct=EBI-719459, EBI-530054; Q96EB6:SIRT1; NbExp=11; IntAct=EBI-719459, EBI-1802965; Q96T88:UHRF1; NbExp=10; IntAct=EBI-719459, EBI-1548946; SUBCELLULAR LOCATION: Nucleus. TISSUE SPECIFICITY: 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. INDUCTION: Its abundance is reduced to non detectable levels at the G0 phase of the cell cycle and is dramatically induced upon entrance into the S-phase of the cell cycle. DOMAIN: The N-terminal part is required for homodimerization and acts as a regulatory domain. 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 (PubMed:21163962). PTM: Sumoylated; sumoylation increases activity. PTM: 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. PTM: 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. PTM: Methylation at Lys-142 by SETD7 promotes DNMT1 proteasomal degradation. PTM: Ubiquitinated by UHRF1; interaction with USP7 counteracts ubiquitination by UHRF1 by promoting deubiquitination and preventing degradation by the proteasome (By similarity). DISEASE: Defects in DNMT1 are the cause of hereditary sensory neuropathy type 1E (HSN1E) [MIM:614116]. A neurodegenerative disorder characterized by adult onset of progressive peripheral sensory loss associated with progressive hearing impairment and early-onset dementia. SIMILARITY: Belongs to the C5-methyltransferase family. SIMILARITY: Contains 2 BAH domains. SIMILARITY: Contains 1 CXXC-type zinc finger. SEQUENCE CAUTION: Sequence=AAD54507.1; Type=Erroneous gene model prediction; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/DNMT1ID40347ch19p13.html";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P26358
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
