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MGP000854

UniProt Annotations

Entry Information
Gene NameDNA (cytosine-5-)-methyltransferase 1
Protein EntryDNMT1_HUMAN
UniProt IDP26358
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=1; IsoId=P26358-1; Sequence=Displayed; Name=2; Synonyms=Dnmt1b; IsoId=P26358-2; Sequence=VSP_005618; Name=3; IsoId=P26358-3; Sequence=VSP_005617;
Catalytic ActivityS-adenosyl-L-methionine + DNA = S-adenosyl-L- homocysteine + DNA containing 5-methylcytosine. {ECO:0000255|PROSITE-ProRule:PRU10018}.
DiseaseCerebellar ataxia, deafness, and narcolepsy, autosomal dominant (ADCADN) [MIM:604121]: 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. {ECO:0000269|PubMed:22328086}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseNeuropathy, hereditary sensory, 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. {ECO:0000269|PubMed:21532572}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DomainThe 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. {ECO:0000269|PubMed:21163962}.
DomainThe N-terminal part is required for homodimerization and acts as a regulatory domain.
FunctionMethylates 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. {ECO:0000269|PubMed:16357870, ECO:0000269|PubMed:18413740, ECO:0000269|PubMed:18754681}.
InductionIts 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.
InteractionO75530:EED; NbExp=3; IntAct=EBI-719459, EBI-923794; Q15910:EZH2; NbExp=8; IntAct=EBI-719459, EBI-530054; P48552:NRIP1; NbExp=3; IntAct=EBI-719459, EBI-746484; Q96EB6:SIRT1; NbExp=11; IntAct=EBI-719459, EBI-1802965; Q96T88:UHRF1; NbExp=12; IntAct=EBI-719459, EBI-1548946;
PtmAcetylation 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. {ECO:0000269|PubMed:19608861, ECO:0000269|PubMed:21947282}.
PtmMethylation at Lys-142 by SETD7 promotes DNMT1 proteasomal degradation. {ECO:0000269|PubMed:18438403, ECO:0000269|PubMed:21151116}.
PtmPhosphorylation 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. {ECO:0000269|PubMed:17081983, ECO:0000269|PubMed:18220336, ECO:0000269|PubMed:18669648, ECO:0000269|PubMed:19690332, ECO:0000269|PubMed:20068231, ECO:0000269|PubMed:21151116, ECO:0000269|PubMed:21406692, ECO:0000269|PubMed:21565170}.
PtmSumoylated; sumoylation increases activity. {ECO:0000269|PubMed:19450230}.
PtmUbiquitinated by UHRF1; interaction with USP7 counteracts ubiquitination by UHRF1 by promoting deubiquitination and preventing degradation by the proteasome. {ECO:0000250}.
Sequence CautionSequence=AAD54507.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
SimilarityBelongs to the class I-like SAM-binding methyltransferase superfamily. C5-methyltransferase family. {ECO:0000255|PROSITE-ProRule:PRU01016}.
SimilarityContains 1 CXXC-type zinc finger. {ECO:0000255|PROSITE-ProRule:PRU00509}.
SimilarityContains 1 DMAP-interaction domain. {ECO:0000305}.
SimilarityContains 1 SAM-dependent MTase C5-type domain. {ECO:0000255|PROSITE-ProRule:PRU01016}.
SimilarityContains 2 BAH domains. {ECO:0000255|PROSITE- ProRule:PRU00370}.
Subcellular LocationNucleus {ECO:0000269|PubMed:12145218}.
SubunitBinds 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. {ECO:0000250, ECO:0000269|PubMed:10888872, ECO:0000269|PubMed:10888886, ECO:0000269|PubMed:10947852, ECO:0000269|PubMed:12145218, ECO:0000269|PubMed:16357870, ECO:0000269|PubMed:19450230, ECO:0000269|PubMed:21163962, ECO:0000269|PubMed:21389349, ECO:0000269|PubMed:21745816, ECO:0000269|PubMed:9302295}.
Tissue SpecificityUbiquitous; 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. {ECO:0000269|PubMed:10325416}.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/DNMT1ID40347ch19p13.html";
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