DNMT3A

CpG methylation is an epigenetic modification that is important for embryonic development, imprinting, and X-chromosome inactivation. Studies in mice have demonstrated that DNA methylation is required for mammalian development. This gene encodes a DNA methyltransferase that is thought to function in de novo methylation, rather than maintenance methylation. The protein localizes to the cytoplasm and nucleus and its expression is developmentally regulated. [provided by RefSeq, Mar 2016]

DNA Methyltransferase 3 Alpha

Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development (PubMed:12138111, PubMed:16357870, PubMed:30478443).

DNA methylation is coordinated with methylation of histones (PubMed:12138111, PubMed:16357870, PubMed:30478443).

It modifies DNA in a non-processive manner and also methylates non-CpG sites (PubMed:12138111, PubMed:16357870, PubMed:30478443).

May preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1 (By similarity).

Plays a role in paternal and maternal imprinting (By similarity).

Required for methylation of most imprinted loci in germ cells (By similarity).

Acts as a transcriptional corepressor for ZBTB18 (By similarity).

Recruited to trimethylated 'Lys-36' of histone H3 (H3K36me3) sites (By similarity).

Can actively repress transcription through the recruitment of HDAC activity (By similarity).

Also has weak auto-methylation activity on Cys-710 in absence of DNA (By similarity).

Aging Source: Ensembl
Cellular response to amino acid stimulus Source: Ensembl
Cellular response to ethanol Source: Ensembl
Cellular response to hypoxia Source: Ensembl
DNA methylation Source: UniProtKB
DNA methylation-dependent heterochromatin assembly Source: Ensembl
DNA methylation involved in embryo development Source: Ensembl
DNA methylation involved in gamete generation Source: Ensembl
Hepatocyte apoptotic process Source: Ensembl
Mitotic cell cycle Source: Ensembl
Negative regulation of transcription by RNA polymerase II Source: BHF-UCL
Neuron differentiation Source: Ensembl
Positive regulation of cell death Source: Ensembl
Regulation of gene expression by genetic imprinting Source: UniProtKB
Response to cocaine Source: Ensembl
Response to drug Source: Ensembl
Response to estradiol Source: Ensembl
Response to ionizing radiation Source: Ensembl
Response to lead ion Source: Ensembl
Response to toxic substance Source: Ensembl
Response to vitamin A Source: Ensembl
Spermatogenesis Source: Ensembl

Nucleus; Cytoplasm; Chromosome. Accumulates in the major satellite repeats at pericentric heterochromatin.

Tatton-Brown-Rahman syndrome (TBRS):
An overgrowth syndrome characterized by a distinctive facial appearance, tall stature and intellectual disability. Facial gestalt is characterized by a round face, heavy horizontal eyebrows and narrow palpebral fissures. Less common features include atrial septal defects, seizures, umbilical hernia, and scoliosis.
Leukemia, acute myelogenous (AML):
A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes.
Heyn-Sproul-Jackson syndrome (HESJAS):
An autosomal dominant form of microcephalic dwarfism. Affected individuals have intrauterine growth retardation, postnatal growth restrictions, proportionate short stature, microcephaly, severe developmental delay and impaired intellectual development. More variable features include sparse hair, short broad metacarpals and phalanges, and mild recurrent infections.

Sumoylated; sumoylation disrupts the ability to interact with histone deacetylases (HDAC1 and HDAC2) and repress transcription.
Auto-methylated at Cys-710: auto-methylation takes place in absence of DNA substrate and inactivates the DNA methyltransferase activity. Inactivation by auto-methylation may be used to inactivate unused DNA methyltransferases in the cell.