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Details on Person UniProt:P26358 DNMT1

Class:Id	ReferenceGeneProduct:403470
_chainChangeLog	chain:1-1616 added on Fri February 6 2015
_displayName	UniProt:P26358 DNMT1
_timestamp	2026-02-20 22:20:47
chain	chain:1-1616
checksum	1E833192D22AFA5B
comment	FUNCTION DNA methyltransferase that methylates CpG residues (PubMed:17200670, PubMed:18754681, PubMed:21745816, PubMed:26070743). Preferentially methylates hemimethylated DNA (PubMed:21745816, PubMed:26070743). Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is essential for epigenetic inheritance (PubMed:17200670, PubMed:21745816). Associates with chromatin during G2 and M phases to maintain DNA methylation independently of replication (PubMed:21745816). It is responsible for maintaining methylation patterns established in development (PubMed:21745816). DNA methylation is coordinated with methylation of histones (PubMed:16357870). Mediates transcriptional repression by direct binding to HDAC2 (PubMed:10888872). 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 (PubMed:18413740). 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).CATALYTIC ACTIVITY a 2'-deoxycytidine in DNA + S-adenosyl-L-methionine = a 5-methyl-2'-deoxycytidine in DNA + S-adenosyl-L-homocysteine + H(+)SUBUNIT 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 (By similarity). Interacts with SIRT7 (By similarity). Interacts with ZNF263; recruited to the SIX3 promoter along with other proteins involved in chromatin modification and transcriptional corepression where it contributes to transcriptional repression (PubMed:32051553). Interacts with L3MBTL3 and DCAF5; the interaction requires DNMT1 methylation at Lys-142 and is necessary to target DNMT1 for ubiquitination by the CRL4-DCAF5 E3 ubiquitin ligase complex and proteasomal degradation (PubMed:29691401). Interacts with PHF20L1; the interaction requires DNMT1 methylation at Lys-142 and protects DNMT1 from ubiquitination and proteasomal degradation (PubMed:24492612).INTERACTION Associates with replication foci during S-phase: recruited to hemimethylated DNA sites via its RFTS domain, which specifically recognizes and binds histone H3 ubiquitinated at 'Lys-14', 'Lys-18' and 'Lys-23' (H3K14ub, H3K18ub and H3K23ub, respectively) (PubMed:29053958). Localized to the perinucleolar region (PubMed:24492612).ALTERNATIVE PRODUCTS 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 RFTS domain specifically recognizes and binds histone H3 monoubiquitinated at two sites, either at 'Lys-14', 'Lys-18' and/or 'Lys-23' (H3K14ub, H3K18ub and H3K23ub, respectively) (PubMed:29053958). These histone marks are present at hemimethylated DNA sites at replication forks and act as docking site for DNMT1 (PubMed:29053958). In absence of H3K14ub, H3K18ub and H3K23ub chromatin marks, the RFTS domain inhibits the DNA methyltransferase activity by forming hydrogen bonds with the catalytic center (PubMed:29053958). Binding to ubiquitinated histones relieves inhibition (PubMed:29053958).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.PTM Sumoylated; sumoylation increases activity.PTM Acetylation on multiple lysines, mainly by KAT2B/PCAF, regulates cell cycle G(2)/M transition (PubMed:21947282). Deacetylation of Lys-1349 and Lys-1415 by SIRT1 increases methyltransferase activity (PubMed:21947282).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 thereby increasing DNMT1 stability.PTM Methylation at Lys-142 by SETD7 is necessary for the regulation of DNMT1 proteasomal degradation.PTM Ubiquitinated by UHRF1; interaction with USP7 counteracts ubiquitination by UHRF1 by promoting deubiquitination and preventing degradation by the proteasome.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the class I-like SAM-binding methyltransferase superfamily. C5-methyltransferase family.
created	[InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35
description	recommendedName: DNA (cytosine-5)-methyltransferase 1 shortName: Dnmt1 ecNumber evidence="26 31"2.1.1.37 alternativeName: CXXC-type zinc finger protein 9 alternativeName: DNA methyltransferase HsaI shortName: DNA MTase HsaI shortName: M.HsaI alternativeName: fullName evidence="37"MCMT
geneName	DNMT1 AIM CXXC9 DNMT
identifier	P26358
isSequenceChanged	FALSE
keyword	3D-structure Acetylation Activator Alternative splicing Chromatin regulator Chromosome Deafness Disease variant DNA-binding Isopeptide bond Metal-binding Methylation Methyltransferase Neuropathy Nucleus Phosphoprotein Proteomics identification Reference proteome Repeat Repressor S-adenosyl-L-methionine Transcription Transcription regulation Transferase Ubl conjugation Zinc Zinc-finger
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20
name	DNMT1
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:5660086] ENSEMBL:ENSG00000130816 DNMT1 [Homo sapiens]
secondaryIdentifier	DNMT1_HUMAN A0AV63 B7ZLW6 Q9UHG5 Q9ULA2 Q9UMZ6
sequenceLength	1616
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:53794] UniProt:P26358-1 DNMT1 [Homo sapiens] [ReferenceIsoform:146466] UniProt:P26358-2 DNMT1 [Homo sapiens] [ReferenceIsoform:146467] UniProt:P26358-3 DNMT1 [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:212181] DNMT1 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:4655353] monoSUMO1-K-DNMT1 [nucleoplasm] [Homo sapiens]
(referenceSequence)	[GroupModifiedResidue:4655391] sumoylated lysine (monoSUMO1 [nucleoplasm]) at unknown position
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