Phospho-Dnmt1 (Tyr399) Antibody - #AF3790

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. Promotes tumor growth.

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 promotes DNMT1 proteasomal degradation.

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

Nucleus.

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.

Homodimer. Forms a stable complex with E2F1, BB1 and HDAC1. Forms a complex with DMAP1 and HDAC2, with direct interaction. Interacts with the PRC2/EED-EZH2 complex. Probably part of a corepressor complex containing ZNF304, TRIM28, SETDB1 and DNMT1. Interacts with UHRF1; promoting its recruitment to hemimethylated DNA. Interacts with USP7, promoting its deubiquitination. Interacts with PCNA. Interacts with MBD2 and MBD3. Interacts with DNMT3A and DNMT3B. Interacts with UBC9. Interacts with CSNK1D (By similarity). Interacts with HDAC1 (By similarity). Interacts with BAZ2A/TIP5 (By similarity). Interacts with SIRT7 (By similarity).

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.

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