DNA (cytosine-5)-methyltransferase 1

Function

DNA methyltransferase that 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. Also required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing.

Classification

Family (Pfam)

PF01426 BAH, PF06464 DMAP_binding, PF00145 DNA_methylase, PF12047 DNMT1-RFD, PF02008 zf-CXXC

InterPro

BAH_dom, BAH_sf, C5-Methyltransferase, C5_DNA_meth_AS, C5_MeTfrase, C5_meth_CS, Cytosine_MeTrfase1_RFD, DMAP1-bd, SAM-dependent_MTases_sf, Znf_CXXC

Functional cluster

Serine/Threonine Protein Kinases

Experimental structures · PDB · 25

• 3EPZ X-ray 2.31A
• 3PTA X-ray 3.60A
• 3SWR X-ray 2.49A
• 4WXX X-ray 2.62A
• 4YOC X-ray 2.92A
• 4Z96 X-ray 2.85A
• 4Z97 X-ray 3.00A
• 5WVO X-ray 2.00A
• 5YDR X-ray 2.00A
• 6K3A X-ray 2.30A
• 6L1F X-ray 1.90A
• 6X9I X-ray 2.20A
• … and 13 more

A predicted model is available from AlphaFold.

Gene Ontology · 27

• GO:0000792 heterochromatin
• GO:0005739 mitochondrion
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0005721 pericentric heterochromatin
• GO:0005657 replication fork
• GO:0003886 DNA (cytosine-5-)-methyltransferase activity
• GO:0003677 DNA binding
• GO:0009008 DNA-methyltransferase activity
• GO:0140258 histone H3K14ub reader activity
• GO:0140254 histone H3K18ub reader activity
• GO:0140257 histone H3K23ub reader activity
• GO:0106222 lncRNA binding
• GO:0008327 methyl-CpG binding
• GO:1990841 promoter-specific chromatin binding
• GO:0008270 zinc ion binding
• GO:0141119 chromosomal DNA methylation maintenance following DNA replication
• GO:0006346 DNA methylation-dependent constitutive heterochromatin formation
• GO:0006351 DNA-templated transcription
• GO:0032259 methylation
• GO:0010629 negative regulation of gene expression
• GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation
• GO:0000122 negative regulation of transcription by RNA polymerase II
• GO:1905460 negative regulation of vascular associated smooth muscle cell apoptotic process
• GO:1905931 negative regulation of vascular associated smooth muscle cell differentiation involved in phenotypic switching
• GO:0010628 positive regulation of gene expression
• GO:1904707 positive regulation of vascular associated smooth muscle cell proliferation

Disease associations

• autosomal dominant cerebellar ataxia, deafness and narcolepsy MONDO:0011397
• hereditary sensory neuropathy-deafness-dementia syndrome MONDO:0013584

Drugs targeting this protein · 2

• DECITABINE inhibitor
• AZACITIDINE inhibitor

Related proteins · sequence + function similarity

• DNA (cytosine-5)-methyltransferase 1 0.96
• DNA (cytosine-5)-methyltransferase 1 0.93
• DNA (cytosine-5)-methyltransferase 1 0.91
• DNA (cytosine-5)-methyltransferase 1.S 0.82
• DNA (cytosine-5)-methyltransferase 1.L 0.81
• DNA (cytosine-5)-methyltransferase 1 0.78
• DNA (cytosine-5)-methyltransferase PliMCI 0.76
• Histone acetyltransferase KAT6B 0.63
• DNA (cytosine-5)-methyltransferase CMT1 0.62
• DNA (cytosine-5)-methyltransferase 4 0.62
• DNA (cytosine-5)-methyltransferase 1B 0.61
• DNA (cytosine-5)-methyltransferase 3 0.61

Co-cited proteins · studied together in the literature

• DNA (cytosine-5)-methyltransferase 1 5 shared papers
• PHD finger protein 20-like protein 1 1 shared papers
• DNA (cytosine-5)-methyltransferase 3B 5 shared papers
• DNA (cytosine-5)-methyltransferase 3A 5 shared papers
• DNA (cytosine-5)-methyltransferase 1 1 shared papers
• DNA sliding clamp PCNA 1 shared papers
• DNA (cytosine-5)-methyltransferase 1.L 1 shared papers
• Retinoblastoma-associated protein 1 shared papers
• SUMO-conjugating enzyme UBC9 1 shared papers
• E3 ubiquitin-protein ligase UHRF1 2 shared papers
• Transcriptional repressor CTCFL 1 shared papers
• Transcriptional repressor CTCF 1 shared papers

Literature · 46 cited papers

• The EGFR-ZNF263 signaling axis silences SIX3 in glioblastoma epigenetically. Oncogene · 2020
• Methylated DNMT1 and E2F1 are targeted for proteolysis by L3MBTL3 and CRL4-DCAF5 ubiquitin ligase. Nat. Commun. · 2018
• Structure of the Dnmt1 reader module complexed with a unique two-mono-ubiquitin mark on histone H3 reveals the basis for DNA methylation maintenance. Mol. Cell · 2017
• Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
• Crystal Structure of Human DNA Methyltransferase 1. J. Mol. Biol. · 2015
• SUMO-2 orchestrates chromatin modifiers in response to DNA damage. Cell Rep. · 2015
• A KRAS-directed transcriptional silencing pathway that mediates the CpG island methylator phenotype. Elife · 2014
• Methyllysine reader plant homeodomain (PHD) finger protein 20-like 1 (PHF20L1) antagonizes DNA (cytosine-5) methyltransferase 1 (DNMT1) proteasomal degradation. J. Biol. Chem. · 2014
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy. Hum. Mol. Genet. · 2012
• SIRT1 deacetylates the DNA methyltransferase 1 (DNMT1) protein and alters its activities. Mol. Cell. Biol. · 2011
• … and 34 more in the literature graph