DNMT3A

Domain

The PWWP domain is essential for targeting to pericentric heterochromatin. It specifically recognizes and binds trimethylated 'Lys-36' of histone H3 (H3K36me3) (By similarity).

Function

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).

Involvement in disease

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.

None

The disease is caused by variants affecting the gene represented in this entry.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

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.

Sequence similarities

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

Tissue specificity

Highly expressed in fetal tissues, skeletal muscle, heart, peripheral blood mononuclear cells, kidney, and at lower levels in placenta, brain, liver, colon, spleen, small intestine and lung.

Cellular localization

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

Alternative names

• DNA (cytosine-5)-methyltransferase 3A
• Dnmt3a
• Cysteine methyltransferase DNMT3A
• DNA methyltransferase HsaIIIA
• DNA MTase HsaIIIA
• M.HsaIIIA
• DNMT3A

Database links

• swissprot:Q9Y6K1

Target type

Proteins

Primary research area

Epigenetics

Molecular weight

101858Da